Choline, a quaternary amine obtained largely from the diet but also synthesized in the brain and, especially, liver, is an essential precursor of the neurotransmitter acetylcholine (ACh) and of the major membrane constituent phosphatidylcholine (PC). Plasma choline concentrations can vary over a fivefold range depending on the choline contents of the foods being digested. Since choline readily crosses the blood–brain barrier (BBB) through an unsaturated facilitated-diffusion system, these plasma changes can produce parallel changes in brain choline levels. In addition, since the enzymes that convert choline to ACh [choline acetyltransferase (ChAT)] and PC's precursor phosphocholine [choline kinase (CK)] are also poorly saturated with their choline substrate, increases in plasma choline can enhance the formation of ACh and phosphocholine, and the release of ACh. The subsequent conversion of phosphocholine to PC is increased if PC's other circulating precursors (uridine and omega-3 fatty acids) are provided. This leads to an increase in the levels of synaptic membrane within the brain. Choline is principally metabolized in the liver to betaine, which provides a source of methyl groups for the regeneration of methionine and S-adenosylmethionine.
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amyloid precursor protein
high-affinity choline transporter
central nervous system
concentrative nucleoside transporter
CTP:phosphocholine cytidylyl transferase
equilibrative nucleoside transporter
flavine adenine dinucleotide
Food and Nutrition Board
generally regarded as safe
luteinizing hormone-releasing hormone
muscarinic acetylcholine receptor
mitogen-activated protein kinase
nicotinic acetylcholine receptor
nicotinamide adenine dinucleotide
nucleoside diphosphate kinase
nerve growth factor
organic cation transporter
protein kinase A
polyunsaturated fatty acid
recommended daily allowance
Abe K, Koqure K, Yamomoto H, Imazawa M, Miyamoto K. 1987. Mechanism of arachidonic acid liberation during ischemia in gerbil cerebral cortex. J Neurochem 48: 503–509.
Absil J, Tuilie M, Roux J-M. 1980. Electrophoretically distinct forms of uridine kinase in the rat. Tissue distribution and age-dependence. Biochem J 185: 273–276.
Acara M, Rennick B. 1973. Regulation of plasma choline by the renal tubule: bidirectional transport of choline. Am J Physiol 225: 1123–1128.
Acara M, Roch-Rammel F, Rennick B. 1979. Bidirectional renal transport of free choline: A micropuncture study. Am J Physiol 236: F112–F118.
Adibhatla RM, Hatcher JF. 2003. Citicoline decreases phospholipase A2 stimulation and hydroxyl radical generation in transient cerebral ischemia. J Neurosci Res 73: 308–315.
Adibhatla RM, Hatcher JF. 2005. Cytidine 5′-diphosphocholine (CDP-choline) in stroke and other CNS disorders. Neurochem Res 30: 15–23.
Adibhatla RM, Hatcher JF, Dempsey RJ. 2001. Effects of citicoline on phospholipid and glutathione levels in transient cerebrala ischemia. Stroke 32: 2376–2381.
Adibhatla RM, Hatcher JF, Larsen EC, Chen X, Sun D, et al. 2006. CDP-choline significantly restores phosphotidylcholine levels by differentially affecting phospholipase A2 and CTP: Phosphocholine cytidylyltransferase after stroke. J Biol Chem 281: 6718–6725.
Agut J, Coviella IL, Wurtman RJ. 1984. Cytidine (5′) diphosphocholine enhances the ability of haloperidol to increase dopamine metabolites in the striatum of the rat and to diminish stereotyped behaviour induced by apomorphine. Neuropharmacology 23: 1403–1406.
Agut J, Ortiz JA, Wurtman RJ. 2000. Cytidine (5′) diphosphocholine modulates dopemine K(+)-evoked release in striatum measured by microdialysis. Ann NY Acad Sci 920: 332–325.
Agut J, Font E, Sacristan A, Ortiz JA. 1983. Effect of oral CDP-choline on acrylamide-induced lesion. Arzneimittelforschung 33: 1029–1033.
Alberghina M, Viola M, Giuffrida AM. 1981. Pool size of CDP-choline in the brain, heart, and lung of normal hypoxic guinea pigs. J Neurosci Res 6: 719–722.
Albright CD, Friedrich CB, Brown EC, Mar MH, Zeisel SH. 1999a. Maternal dietary choline availability alters mitosis, apoptosis and the localization of TOAD-64 protein in the developing fetal rat septum. Brain Res Dev Brain Res 115: 123–129.
Albright CD, Tsai AY, Friedrich CB, Mar MH, Zeisel SH. 1999b. Choline availability alters embryonic development of the hippocampus and septum in rat. Brain Res Dev Brain Res 113: 13–20.
Albuquerque EX, Pereira EFR, Braga MFM, Alkondon M. 1998. Contribution of nicotinic receptors to the function of synapses in the central nervous system: The action of choline as a selective agonist of α7 receptors. J Physiol (Paris) 92: 309–316.
Alkan T, Kahveci N, Goren B, Korfali E, Ozluk K. 2001. Ischemic brain injury model caused by interrupted versus uninterrupted occlusion in hypotensive rats with subarachnoid hemorrhage: Neuroprotective effects of citicoline. Arch Physiol Biochem 109: 161–167.
Alkondon M, Albuquerque EX. 2006. Subtype-specific inhibition of nicotinic acetylcholine receptors by choline: A regulatory pathway. J Pharmacol Exp Ther 318: 268–275.
Alkondon M, Braga MFM, Pereria EFR, Maelicke A, Albuquerque EX. 2000. Alpha7 nicotinic acetylcholine receptors and modulation of gabaergic synaptic transmission in the hippocampus. Eur J Pharmacol 393: 59–67.
Alkondon M, Pereira EFR, Cortes WS, Maelicke A, Albuquergue EX. 1997. Choline is a selective agonist of alpha7 nicotinic acetylcholine receptors in the rat brain neurons. Eur J Neurosci 9: 2734–2742.
Allen DD, Smith QR. 2001. Characterization of the blood–brain barrier choline transporter using the in situ rat brain perfusion technique. J Neurochem 76: 1032–1041.
Altura BA. 1978. Role of spleen in choline stimulation of reticoendothelial system and resistance to acute haemorrhage. Proc Soc Exp Biol Med 158: 77–80.
Alvarez XA, Sampedro C, Lozano R, Cacabelos R. 1999. Citicoline protects hippocampal neurons against apoptosis induced by brain beta-amyloid deposits plus cerebral hypoperfusion in rats. Methods Find Exp Clin Pharmacol 21: 535–540.
Alvarez XA, Laredo M, Corzo D, Fernadez-Novoa L, Mouzo R, et al. 1997. Citicoline improves memory performance in elderly subjects. Methods Find Exp Clin Pharmacol 19: 201–210.
Anderson CM, Baldwin SA, Young JD, Cass CE, Parkinson FE. 1999b. Distribution of mRNA encoding a nitrobenzylthioinosine-insensitive nucleoside transporter (ENT2) in rat brain. Brain Res Mol Brain Res 70: 293–297.
Anderson CM, Xiong W, Geiger JD, Young JD, Cass CE, et al. 1999a. Distribution of equilibrative, nitrobenzylthioinosine-insensitive nucleoside transporters (ENT1) in rat brain. J Neurochem 73: 867–873.
Anderson EP. 1973. Nucleoside and nucleotide kinases. In: The Enzymes, Boyer PD, editor. New York: Academic Press; pp. 49–96.
Andersen M, Overgaard K, Meden P, Boysen G, Choi SC. 1999. Effects of citicoline combined with thrombolytic therapy in a rat embolic stroke model. Stroke 30: 1464–1471.
Ansell GB, Spanner S. 1971. Studies on the origin of choline in the brain of the rat. Biochem J 122: 741–750.
Ansell GB, Spanner S. 1974. The inhibition of brain choline kinase by hemicholinium-3. J Neurochem 22: 1153–1155.
Anton V. 1954. Differencias en el mecanismo hipotensor de la acetylcolina y colina. Res Esp Fisiol 10: 179–188.
Aoyama C, Liao H, Ishidate K. 2004. Structure and function of choline kinase isoforms in mammalian cells. Prog Lipid Res 43: 266–281.
Aoyama C, Nakashima K, Matsui M, Ishidate K. 1998. Molecular cloning of mouse choline kinase and choline/ethanolamine kinase: Their sequence comparison to the respective rat homologs. Biochim Biophys Acta 1393: 179–185.
Aoyama C, Yamazaki N, Terada H, Ishidate K. 2000. Structure and characterization of the genes for murine choline/ethanolamine kinase isozymes alpha and beta. J Lipid Res 41: 452–464.
Apparsundaram S, Ferguson SM, Blakely RD. 2001. Molecular cloning and characterization of a murine hemicholinium-3-sensitive choline transporter. Biochem Soc Trans 29: 711–716.
Apparsundaram S, Ferguson SM, George AL Jr, Blakely RD. 2000. Molecular cloning of a human, hemicholinium-3-sensitive choline transporter. Biochem Biophys Res Commun 276: 862–867.
Apparsundaram S, Martinez V, Parikh V, Kozak R, Sarter M. 2005. Increased capacity and density of choline transporters situated in synaptic membranes of the right medial prefrontal cortex of attentional task-performing rats. J Neurosci 25: 3851–3856.
Araki H, Karasawa Y, Nojiiri M, Aihara H. 1988. Effects of various classes of drugs on complete ischemia induced by decapitation and cyanide intoxication in mice. Methods Find Exp Clin Pharmacol 10: 349–359.
Araki W, Wurtman RJ. 1997. Control of membrane phosphatidylcholine biosynthesis by diacylglycerol levels in neuronal cells undergoing neurite outgrowth. Proc Natl Acad Sci USA 94: 11946–11950.
Araki W, Wurtman RJ. 1998. How is membrane phospholipid biosynthesis controlled in neural tissues? J Neurosci Res 51: 667–674.
Arslan BY, Ulus IH, Savci V, Kiran BK. 1991. Effects of intracerebroventricular injected choline on cardiovascular functions and sympathoadrenal activity. J Cardiovasc Pharmacol 17: 814–821.
Ataus SA, Onal MZ, Ozdem SS, Locke KW, Balkan S. 2004. The effects of citicoline and lamotrigine alone and in combination following permanent middle arter cerebral artery occlusion in rats. Int J Neurosci 114: 183–196.
Babb SM, Ke Y, Lange N, Kaufman MJ, Renshaw PF, et al. 2004. Oral choline increases choline metabolites in human brain. Psychiatry Res 130: 1–9.
Bacq ZM, Brown GL. 1937. Pharmacological experiments on mammalian voluntary muscle, in relation to the theory of chemical transmission. J Physiol (London) 89: 45–60.
Baldwin SA, Beal PR, Yao SYM, King AE, Cass CE, et al. 2004. The equilibrative nucleoside transporter family, SLC29. Pflugers Arch 447: 735–743.
Barak AJ, Tuma DJ. 1983. Betaine, metabolic by-product or vital methylating agent? Life Sci 32: 771–774.
Barak AJ, Beckenhauer HC, Tuma DJ. 1996. Betaine, ethanol, and the liver: A review. Alcohol 4: 395–398.
Barrachina M, Dominguez I, Ambrosio S, Secades J, Lozano R, et al. 2003. Neuroprotective effect of citicoline in 6-hydroxydopamine-lesioned rats and in 6-hydroxydopamine-treated SH-SY5Y human neuroblastoma cells. J Neurological Sci 215: 105–110.
Bartus RT, Dean RL, Goas JA, Lippa AS. 1980. Age-related changes in passive avoidance retention: Modulation with dietary choline. Science 209: 301–303.
Baskaya MK, Dogan A, Rao AM, Dempsey RJ. 2000. Neuroprotective effects of citicoline on brain edema and blood–brain barrier breakdown after traumatic brain injury. J Neurosurg 92: 448–452.
Benishin CG, Carroll PT. 1981. Acetylation of choline and homocholine by membrane-bound choline-O-acetyltransferase in mouse forebrain nerve endings. J Neurochem 36: 732–740.
Benishin CG, Carroll PT. 1983. Multiple forms of choline-O-acetyltransferase in mouse and rat brain: Solubilization and characterization. J Neurochem 41: 1030–1039.
Berg P, Joklik WK. 1954. Enzymatic phosphorylation of nucleoside diphosphates. J Biol Chem 210: 617–672.
Bernheim F, Bernheim MLC. 1933. Oxidation of acetylcholine by tissues. Am J Physiol 104: 438–440.
Berse B, Szczecinska W, Lopez-Coviella I, Madziar B, Zemelko V, et al. 2005. Expression of high affinity choline transporter during mouse development in vivo and its upregulation by NGF and BMP-4 in vitro. Brain Res Dev Brain Res 157: 132–140.
Bierkamper GG, Goldberg AM. 1979. The effect of choline on the release of acetylcholine from the neuromuscular junction. In: Nutrition and the Brain, Vol. 5, Barbeau A, Growdon JH, Wurtman RJ, editors. New York: Raven Press; pp. 243–251.
Bierkamper GG, Goldberg AM. 1980. Release of acetylcholine from the vascular perfused rat phrenic nerve-hemidiaphragm. Brain Res 202: 234–247.
Birks RI, MacIntosh FC. 1961. Acetylcholine metabolism of a sympathetic ganglion. Can J Biochem Physiol 39: 787–827.
Blusztajn JK, Wurtman RJ. 1981. Choline biosynthesis by a preparation enriched in synaptosomes from rat brain. Nature 290: 417–418.
Blusztajn JK, Wurtman RJ. 1983. Choline and cholinergic neurons. Science 221: 614–620.
Blusztajn JK, Zeisel SH, Wurtman RJ. 1979. Synthesis of lecithin (phosphatidylcholine) from phosphatidylethanolamine in bovine brain. Brain Res 179: 319–327.
Blusztajn JK, Zeisel SH, Wurtman RJ. 1982. Phospholipid methylation and cholinergic neurons. In: Biochemistry of S-Adenosylmethionine and Related Compounds. Borchardt R, Usdin E, Creveling C, editors. London: MacMillan Press; pp. 155–164.
Blusztajn JK, Lopez Gonzalez-Coviella I, Logue M, Growdon JH, Wurtman RJ. 1990. Levels of phospholipid catabolic intermediates, glycerophosphocholine and glycerophosphoethanolamine, are elevated in brains of Alzheimer's disease but not of Down's syndrome patients. Brain Res 536: 240–244.
Blusztajn JK, Holbrook PG, Lakher M, Liscovitch M, Maire JC, et al. 1986. Autocannibalism of membrane choline-phospholipids: Physiology and pathology. Psychopharmacol Bull 22: 781–786.
Boismare F, Le Poncin M, Lefrancois M, Lecordier JC. 1978. Action of cytidine diphosphocholine on functional and hemodynamic effects of cerebral ischemia of cats. Pharmacology 17: 15–20.
Boismare F, Le Poncin M, Lefrancois J, Hacpille L, Marchand JC. 1977. Effect of cytidine diphosphocholine on hemodynamic, functional as and biochemical consequences of cranio-cervical trauma in rat. Therapie 32: 345–354.
Borkenhagen LF, Kennedy EP, Fielding L. 1961. Enzymatic formation and decarboxylation of phosphatidylserine. J Biol Chem 236:PC28–PC30.
Boswell K, Koskelo EK, Carl L, Glaza S, Hensen DJ, et al. 1996. Preclinical evaluation of single-cell oils that are highly enriched with arachidonic acid and docosahexaenoic acid. Food Chem Toxicol 34: 585–593.
Botticelli LJ, Lytle LD, Wurtman RJ. 1977. Choline-induced attenuation of morphine analgesia in the rat. Commun Psychopharmacol 1: 519–523.
Boyd WD, Graham-White J, Blackwood G, Glen I, McQueen J. 1977. Clinical effects of choline in Alzheimer senile dementia. Lancet 2: 711.
Bremer J, Greenberg DM. 1960. Biosynthesis of choline in vitro. Biochim Biophys Acta 46: 205.
Buchman AL, Jenden D, Roch M. 1999. Plasma free, phospholipid-bound and urinary free choline all decrease during a marathon run and may be associated with impaired performance. J Am Coll Nutr 18: 598–601.
Buchman AL, Jenden D, Suki WN, Roch M. 2000b. Changes in plasma free and phospholipid-bound choline concentrations in chronic hemodialysis patients. J Ren Nutr 10: 133–138.
Buchman AL, Awal M, Jenden D, Roch M, Kang SH. 2000a. The effects of lecithin supplementation on plasma choline concentrations during a marathon. J Am Coll Nutr 19: 768–770.
Buchman AL, Jenden DJ, Moukarzel AA, Roch M, Rice KM, et al. 1994. Choline pharmacokinetics during intermittent intravenous choline infusion in human subjects. Clin Pharmacol Ther 55: 277–283.
Buchman AL, Sohel M, Moukarzel A, Bryant D, Schanler R, et al. 2001. Plasma choline in normal newborns, infants, toddlers, and in very-low-birth-weight neonates requiring total parenteral nutrition. Nutrition 17: 18–21.
Burt AM, Brody SA. 1975. The measurement of choline kinase activity in rat brain: The problem of alternate pathways of ATP metabolism. Anal Biochem 65: 215–224.
Busch AE, Karbach U, Miska D, Gorboulev V, Akhoundova A, et al. 1998. Human neurons express the polyspecific cation transporter hOCT2, which translocates monoamine neurotransmitters, amantadine, and memantine. Mol Pharmacol 54: 342–352.
Busch AE, Quester S, Ulzheimer JC, Waldegger S, Gorboulev V, et al. 1996. Electrogenic properties and substrate specificity of the polyspecific rat cation transporter rOCT1. J Biol Chem 271: 32599–32604.
Butler M, Morell P. 1983. The role of phosphatidylserine decarboxylase in brain phospholipid metabolism. J Neurochem 41: 1445–1454.
Canellakis ES. 1957. Pyrimidine metabolism. II. Enzymatic pathways of uracil anabolism. J Biol Chem 227: 329–338.
Cansev M. 2006. Uridine and cytidine in the brain. Their transport and utilization. Brain Res Brain Res Rev 52: 389–397.
Cansev M, Wurtman RJ.2005. Exogenous cytidine-5′-diphosphocholine increases brain cytidine-5′-diphosphocholine levels in gerbils. 20th Biennial Meeting of the ISN-ESN Abstracts, Innsbruck, Austria, 21–26 August 2005. J Neurochem 94 (Suppl. 2): 105–106.
Cansev M, Wurtman RJ. 2006. Aromatic amino acids in the brain. In: Handbook of Neurochemistry and Molecular Neurobiology, 3rd edn., Vol. 6, Chapter 3. Lajtha A, editor. New York: Kluwer Academic/Plenum Publishers (in press).
Cansev M, Watkins CJ, van der Beek EM, Wurtman RJ. 2005. Oral uridine-5′-monophosphate (UMP) increases brain CDP-choline levels in gerbils. Brain Res 1058: 101–108.
Cansev M, Wurtman RJ, Ulus IH, Watkins CJ, Wang L, 2006. Characterization of polyunsaturated fatty acids that affect synaptic proteins and phospholipids in gerbil brain. Society for Neuroscience Abstracts, Atlanta, Georgia, 14–18 October.
Cao D, Li M, Xue R, Zheng W, Liu Z, et al. 2005. Chronic administration of ethyl docosahexanoate decreases mortality and cerebral edema in ischemic gerbils. Life Sci 78: 74–81.
Cao D, Zhou C, Sun L, Xue R, Xu J, et al. 2006. Chronic administration of ethyl docosahexanoate reduces gerbil brain eicosanoid productions following ischemia and reperfusion. J Nutr Biochem 17: 234–241.
Cao ZM, Kanfer JN. 1995. Partial purification of two forms of choline kinase and separation of choline kinase from sphingosine kinase of rat brain. Neurochem Res 6: 643–649.
Caputi AP, Brezenoff HE. 1980. Cardiovascular effects produced by choline injected into the lateral cerebral ventricle of the unanesthetized rat. Life Sci 26: 1029–1036.
Carriere JL, El-Fakanay EE. 2000. Choline is a full against in inducing activation of neuronal nitric oxide synthase via the muscarinic M1 receptor. Pharmacology 60: 82–89.
Caulfield MP, Birdsall NJM. 1998. International Union of Pharmacology. XVII. Classification of muscarinic acetylcholine receptors. Pharmacol Rev 50: 279–290.
Cavun S, Savci V. 2004. CDP-choline increase plasma ACTH and potentiates the stimulated release of GH, TSH and LH: The cholinergic involvement. Fundam Clin Pharmacol 18: 513–523.
Cavun S, Savci V, Ulus IH. 2004. Centrally injected CDP-choline increases plasma vasopressin levels by central cholinergic activation. Fundam Clin Pharmacol 18: 71–77.
Cermak JM, Holler T, Jackson DA, Blusztajn JK. 1998. Prenatal availability of choline modifies development of the rat hippocampal cholinergic system. FASEB J 12: 349–357.
Cermak JM, Holler T, Jackson DA, Blusztajn JK. 1999. Prenatal availability of choline alters the development of acetylcholinesterase in the rat hippocampus. Dev Neurosci 21: 94–104.
Chabot GG, Bouchard J, Momparler RL. 1983. Kinetics of deamination of 5-aza-2′-deoxycytidine and cytosine arabinoside by human liver cytidine deaminase and its inhibition by 3-deazauridine, thymidine or uracil arabinoside. Biochem Pharmacol 32: 1327–1328.
Chang HC, Gaddum JH. 1933. Choline esters in tissue extracts. J Physiol (London) 79: 255–285.
Chern M-K, Pietruszko R. 1995. Human aldehyde dehydrogenase E3 isozyme is a betaine aldehyde dehydrogenase. Biochem Biophys Res Commun 213: 561–568.
Choy PC, Paddon HB, Vance DE. 1980. An increase in cytoplasmic CTP accelerates the reaction catalyzed by CTP: Phosphocholine cytidylyltransferase in poliovirus-infected HeLa cells. J Biol Chem 255: 1070–1073.
Clark WM, Williams BJ, Selzer KA, Zweifler RM, Sabounjian LA, et al. 1999. A randomized efficacy trial of citicoline in patients with acute ischemic stroke. Stroke 30: 2592–2597.
Cohen BM, Renshaw PF, Stoll AL, Wurtman RJ, Yurgelun-Todd D, et al. 1995. Decreased brain choline uptake in older adults. An in vivo proton magnetic resonance spectroscopy study. JAMA 274: 902–907.
Cohen EL, Wurtman RJ. 1975. Brain acetylcholine: Increase after systemic choline administration. Life Sci 16: 1095–1102.
Cohen EL, Wurtman RJ. 1976. Brain acetylcholine: Control by dietary choline. Science 191: 561–562.
Coleman P, Federoff H, Kurlan R. 2004. A focus on the synapse for neuroprotection in Alzheimer disease and other dementias. Neurology 63: 1155–1162.
Coleman R, Bell RM. 1977. Phospholipid synthesis in isolated fat cells. Studies of microsomal diacylglycerol cholinephosphotransferase and diacylglycerol ethanolaminephosphotransferase activities. J Biol Chem 252: 3050–3056.
Conlay LA, Sabounjian LA, Wurtman RJ. 1992. Exercise and neuromuscular mediators: Choline and acetylcholine in marathon runners. Int J Sports Med 13: S141–142.
Conlay LA, Wurtman RJ, Blusztajn K, Coviella IL, Maher TJ, et al. 1986. Decreased plasma choline concentrations in marathon runners. N Engl J Med 315: 892.
Contreras MA, Greiner RS, Chang MC, Myers CS, Salem N Jr, et al. 2000. Nutritional deprivation of alpha-linolenic acid decreases but does not abolish turnover and availability of unacylated docosahexaenoic acid and docosahexaenoyl-CoA in rat brain. J Neurochem 75: 2392–2400.
Cornell R. 1989. Chemical cross-linking reveals a dimeric structure for CTP: Phosphocholine cytidylyltransferase. J Biol Chem 264: 9077–9082.
Cornell RB. 1992. Cholinephosphotransferase from mammalian sources. Methods Enzymol 209: 267–272.
Cornell RB, Northwood IC. 2000. Regulation of CTP: Phosphocholine cytidylyltransferase by amphitropism and relocalization. Trends Biochem Sci 25: 441–447.
Cornford EM, Oldendorf WH. 1975. Independent blood–brain barrier transport systems for nucleic acid precursors. Biochim Biophys Acta 394: 211–219.
Cornford EM, Braun LD, Oldendorf WH. 1978. Carrier mediated blood–brain barrier transport of choline and certain choline analogs. J Neurochem 30: 299–308.
Costa LG, Murphy SD. 1984. Interaction of choline with nicotinic and muscarinic cholinergic receptors in rat brain in vitro. Clin Exp Pharmacol Physiol 6: 649–654.
Coutcher JB, Cawley G, Wecker L. 1992. Dietary choline supplementation increases the density of nicotine binding sites in rat brain. J Pharmacol Exp Ther 262: 1128–1132.
Crews FT, Hirata F, Axelrod J. 1980. Identification and properties of methyltransferases that synthesize phosphatidylcholine in rat brain synaptosomes. J Neurochem 34: 1491–1498.
Cuevas J, Roth AL, Berg DK. 2000. Two distinct classes of functional α7-containing nicotinic receptor on rat superior cervical ganglion. J Physiol 525: 735–746.
Cui Z, Vance JE, Chen MH, Voelker DR, Vance DE. 1993. Cloning and expression of a novel phosphatidylethanolamine N-Methyltransferase. A specific biochemical and cytological marker for a unique membrane fraction in rat liver. J Biol Chem 268: 16655–16663.
da Costa K-A, Badea M, Fischer LM, Zeisel SH. 2004. Elevated serum creatine phosphokinase in choline-deficient humans. Am J Clin Nutr 80: 163–170.
da Costa KA, Kozyreva OG, Song J, Galanko JA, Fischer LM, et al. 2006. Common genetic polymorphisms affect the human requirement for the nutrient choline. FASEB J 20: 1336–1344.
Dale HH. 1914. The action of certain esters and ethers of choline, and their relation to muscarine. J Pharmacol Exp Ther 6: 147–190.
Damaj MI, Meyer EM, Martin BR. 2000. The antinociceptive effects of alpha7 nicotinic agonists in an acute pain model. Neuropharmacology 39: 2785–2791.
Danne O, Lueders C, Storm C, Frei U, Mockel M. 2005. Whole-blood hypercholinemia and coronary instability and thrombosis. Clin Chem 51: 1315–1317.
Danne O, Mockel M, Lueders C, Mugge C, Zschunke GA, et al. 2003. Prognostic implications of elevated whole blood choline levels in acute coronary syndromes. Am J Cardiol 91: 1060–1067.
Darios F, Davletov B. 2006. Omega-3 and omega-6 fatty acids stimulate cell membrane expansion by acting on syntaxin 3. Nature 440: 813–817.
Davalos A, Castillo J, Alvarez-Sabin J, Sacades JJ, Mercadal J, et al. 2002. Oral citicoline in acute ischemic stroke: An individual patient data pooling analysis of clinical trials. Stroke 33: 2850–2857.
Davis RL, Mohs RC, Tinklenberg LA, Hollister LE, Pfefferbaum A, et al. 1980. Cholinomimetics and memory: Effect of choline chloride. Arch Neurol 37: 49–51.
de la Huerga J, Popper H. 1951. Urinary excretion of choline metabolites following choline administration to normals and patients with hepatobiliary diseases. J Clin Invest 30: 463–470.
Del Castillo J, Katz B. 1957. Interaction at end-plate receptors between different choline derivatives. Proc R Soc Lond B Biol Sci 146: 369–381.
Dempsey RJ, Raghavendra Rao VL. 2003. Cytidinediphosphocholine treatment to decrease traumatic brain injury-induced hippocampal neuronal death, cortical contusion volume, and neurological dysfunction in rats. J Neurosurg 98: 867–873.
Deutsch J, Rapoport SI, Purdon AD. 1997. Relation between free fatty acid and acyl-CoA concentrations in rat brain following decapitation. Neurochem Res 22: 759–765.
Diamond I. 1971. Choline metabolism in brain. The role of choline transport and the effects of phenobarbital. Arch Neurol 24: 333–339.
Dieterich HA, Lindmar R, Loffelholz K. 1978. The role of choline in the release of acetylcholine in isolated hearths. Naunyn-Schmiedeberg's Arch Pharmacol 301: 207–215.
Dixon CE, Ma X, Marion DW. 1997. Effects of CDP-choline treatment on neurobehavioral deficits after TBI and on hippocampal and neocortical acetylcholine release. J Neurotrauma 14: 161–169.
Dobransky T, Rylett RJ. 2005. A model for dynamic regulation of choline acetyltransferase by phosphorylation. J Neurochem 95: 305–313.
Dobransky T, Davis WL, Rylett RJ. 2001. Functional characterization of phosphorylation of 69-kDa human choline acetyltransferase at serine 440 by protein kinase C. J Biol Chem 276: 22244–22250.
Dobransky T, Brewer D, Lajoie G, Rylett RJ. 2003. Phosphorylation of 69-kDa choline acetyltransferase at threonine 456 in response to amyloid-β peptide 1–42. J Biol Chem 278: 5883–5893.
Dobransky T, Davis WL, Xiao GH, Rylett RJ. 2000. Expression, purification and characterization of recombinant human choline acetyltransferase: Phosphorylation of the enzyme regulates catalytic activity. Biochem J 349: 141–151.
Dobransky T, Doherty-Kirby A, Kim A-R, Brewer D, Lajoie G, et al. 2004. Protein kinase C isoforms differentially phosphorylate human choline acetyltransferase regulating its catalytic activity. J Biol Chem 279: 52059–52068.
Dolezal V, Tucek S. 1982. Effects of choline and glucose on atropine-induced alterations of acetylcholine synthesis and content in the caudate nuclei of rats. Brain Res 240: 285–293.
Dorman RV, Dabrowiecki Z, Horrocks LA. 1983. Effects of CDPcholine and CDPethanolamine on the alterations in rat brain lipid metabolism induced by global ischemia. J Neurochem 40: 276–279.
Eder-Colli L, Amato S, Froment Y. 1986. Amphiphilic and hydrophilic forms of choline-O-acetyltransferase in cholinergic nerve endings of the Torpedo. Neuroscience 19: 275–287.
Farber SA, Savci V, Wei A, Slack BE, Wurtman RJ. 1996. Choline's phosphorylation in rat striatal slices is regulated by the activity of cholinergic neurons. Brain Res 723: 90–99.
Feldberg W, Vartiainen A. 1934. Further observation on the physiology and pharmacology of a sympathetic ganglion. J Physiol (London) 83: 103–128.
Ferguson SG, Diksic M, Collier B. 1991. Stereospecificity of high- and low-affinity transport of choline analogues into rat cortical synaptosomes. J Neurochem 57: 915–921.
Ferguson SM, Blakely RD. 2004. The choline transporter resurfaces: New roles for synaptic vesicles? Mol Interv 4: 22–37.
Ferguson SM, Savchenko V, Apparsundaram S, Zwick M, Wright J, et al. 2003. Vesicular localization and activity-dependent trafficking of presynaptic choline transporters. J Neurosci 23: 9697–9709.
Fernstrom JD, Wurtman RJ. 1971. Brain serotonin content: Physiological dependence on plasma tryptophan levels. Science 173: 149–152.
Ferreira A, Rapoport M. 2002. The synapsins: Beyond the regulation of neurotransmitter release. Cell Mol Life Sci 59: 589–595.
Flentge F, Hajonides-van der Meulen WM, Lakke JP, Teelken AW. 1984. CSF choline levels in groups of patients with cranial trauma or extrapyramidal disorders. J Neurol Neurosurg Psychiatry 47: 207–209.
Fox JM, Betzing H, Lekim D. 1979. Pharmacokinetics of orally ingested phosphatidylcholine. In: Nutrition and Brain, Vol. 5. Wurtman RJ, Wurtman JJ, editors. New York: Raven Press; pp. 95–108.
Frederickson RCA, Pinsky C. 1975. Effects of cholinergic and anticholinergic drugs and a partial cholinergic agonist on the development and expression of physical dependence on morphine in rats. J Pharmacol Exp Ther 193: 44–55.
Friedrich A, George RL, Bridges CC, Prasad PD, Ganapathy V. 2001. Transport of choline and its relationship to the expression of the organic cation transporters in a rat brain microvessel endothelial cell line (RBE4). Biochim Biophys Acta 1512: 299–307.
Friedrich A, Prasad PD, Freyer D, Ganapathy V, Brust P. 2003. Molecular cloning and functional characterization of the OCTN2 transporter at the RBE4 cells, an in vitro model of the blood–brain barrier. Brain Res 968: 69–79.
Froguel P, McGarry JD. 1997. Fine chromosome mapping of the genes for human liver and muscle carnitine palmitoyltransferase I (CPT1A and CPT1B). Genomics 40: 209–211.
Fujita A, Kurachi Y. 2000. SAP family proteins. Biochem Biophys Res Commun 269: 1–6.
Futterman S, Andrews JS. 1964. The fatty acid composition of human retinal vitamin A ester and the lipids of human retinal tissue. Invest Ophthalmol 3: 441–444.
Galletti P, De Rosa M, Cotticelli MG, Morana A, Vaccaro R, et al. 1991. Biochemical rationale for the use of CDPcholine in traumatic brain injury: Pharmacokinetics of the orally administered drug. J Neurol Sci 103: 19–25.
Gates J Jr, Ferguson SM, Blakely RD, Apparsundaram S. 2004. Regulation of choline transporter surface expression and phosphorylation by protein kinase C and protein phosphatase 1/2A. J Pharmacol Exp Ther 310: 536–545.
Genchev DD, Mandel P. 1974. CTP synthetase activity in neonatal and adult rat brain. J Neurochem 22: 1027–1030.
Giacobini E. 2003. Cholinesterases: New roles in brain function and in Alzheimer's disease. Neurochem Res 28: 515–522.
Golczewski JA, Hiramoto RN, Chanta VK. 1982. Enhancement maze learning in old C57BL/6 mice by dietary lecithin. Neurobiol Aging 3: 223–226.
Goldberg WJ, Dorman RV, Dabrowiecki Z, Horrocks LA. 1985. The effects of ischemia and CDPamines on Na+, K+-ATPase and acetylcholinesterase activities in rat brain. Neurochem Pathol 3: 237–248.
Gonzales-Rubio JM, Rojo J, Tapia L, Maneu V, Mulet J, et al. 2006. Activation and blockade by choline α7 and α3β4 nicotinic receptors expressed in oocytes. Eur J Pharmacol 535: 53–60.
Goracci G, Francescangeli E, Horrocks LA, Porcelatti G. 1981. The reverse reaction of cholinephosphotransferase in rat brain microsomes. A new pathway for degradation of phosphatidylcholine. Biochim Biophys Acta 664: 373–379.
Goracci G, Francescangeli E, Horrocks LA, Porcelatti G. 1986. A comparison of the reversibility of phosphoethanolamine transferase and phosphocholine transferase in rat brain microsomes. Biochim Biophys Acta 876: 387–391.
Gorboulev V, Ulzheimer JC, Akhoundova A, Ulzheimer-Teuber I, Karbach U, et al. 1997. Cloning and characterization of two human polyspecific organic cation transporters. DNA Cell Biol 16: 871–881.
Gray JH, Owen RP, Giacomini KM. 2004. The concentrative nucleoside transporter family, SLC28. Pflugers Arch 447: 728–734.
Greenberg N, Schumm DE, Webb TE. 1977. Uridine kinase activities and pyrimidine nucleoside phosphorylation in fluoropyrimidine-sensitive and -resistant cell lines of the Novikoff hepatoma. Biochem J 164: 379–387.
Greenwald BS, Edasery J, Mohs RC, Shah N, Trigos GG, et al. 1985. Red blood cell choline. I: Choline in Alzheimer's disease. Biol Psychiatry 20: 367–374.
Griffith DA, Jarvis SM. 1996. Nucleoside and nucleobase transport systems of mammalian cells. Biochim Biophys Acta 1286: 153–181.
Grundemann D, Schechinger B, Rappold GA, Schomig E. 1998. Molecular identification of the corticosterone-sensitive extraneuronal catecholamine transporter. Nat Neurosci 1: 349–352.
Grundemann D, Gorboulev V, Gambaryan S, Veyhl M, Koepsell H. 1994. Drug excretion mediated by a new prototype of polyspecific transporter. Nature 372: 549–552.
Guo-Ross SX, Clark S, Montoya DAC, Jones KH, Obernier J, et al. 2002. Prenatal choline supplementation protects against postnatal neurotoxicity. J Neurosci 22:RC195.
Gurun MS, Millington WR, Ulus IH. 2003. Choline potentiates the pressor response evoked by glycyl-glutamine or naloxone in haemorrhaged rats. Clin Exp Pharmacol Physiol 30: 640–642.
Gurun MS, Savci V, Ulus IH. 1997a. Intracerebroventricular choline reverses hypotension induced by acute chemical sympathectomy. J Auton Pharmacol 17: 155–163.
Gurun MS, Ilcol YO, Taga Y, Ulus IH. 2002. Hyperglycemia induced by intracerebroventricular choline: Involvement of the sympatho-adrenal system. Eur J Pharmacol 438: 197-205.
Gurun MS, Savci V, Ulus IH, Kiran BK. 1997b. Centrally administered choline increases plasma prolactin levels in conscious rats. Neurosci Lett 232: 79–82.
Guyenet P, Lefresne P, Rossier J, Beaujouan JC, Glowinski J. 1973. Inhibition by hemicholinium-3 of (14C) acetylcholine synthesis and (3H) choline high-affinity uptake in rat striatal synaptosomes. Mol Pharmacol 9: 630–639.
Haberberger RV, Pfeil U, Lips KS, Kummer W. 2002. Expression of the high-affinity choline transporter, CHT1, in the neuronal and non-neuronal cholinergic system of human and rat skin. J Invest Dermatol 119: 943–948.
Haga T, Noda H. 1973. Choline uptake systems of rat brain synaptosomes. Biochim Biophys Acta 291: 564–575.
Hamdorf G, Cervos-Navarro J. 1990. Study of the effects of oral administration of CDP-choline on open-field behaviour under conditions of chronic hypoxia. Arzneimittelforschung 40: 519–522.
Hamdorf G, Cervos-Navarro J. 1991. Therapeutics effect of orally applied cytidine diphosphate choline in mild and severe degrees of normobaric and normocapnic degrees of hypoxia of rats. Arzneimittelforschung 41: 1206–1210.
Hamdorf G, Cervos-Navarro J, Muller R.1992. Increase of survival time in experimental hypoxia by cytidine diphosphate choline. Arzneimittelforschung 42: 421–424.
Hamurtekin E, Gurun MS. 2006. The antinociceptive effects of centrally administered CDP-choline on acute pain models in rats: The involvement of cholinergic system. Brain Res 1117: 92-100.
Harris CM, Dysken MW, Fovall P, Davis JM. 1983. Effect of lecithin on memory in normal adults. Am J Psychiatry 140: 1010–1012.
Harris WS. 2005. Omega-3 fatty acids. In: Encyclopedia of Dietary Supplements, Coates, PM, Blackman MR, Cragg GM, Levine M, Moss J, White JD, editors. New York: Marcel Dekker; pp. 493–504.
Hasegawa Y, Kunihara M, Maruyama Y. 1982. Determination of picomole amounts of choline and acetylcholine in blood by gas chromatography-mass spectrometry equipped with a newly improved pyrolyzer. J Chromatogr 239: 335–342.
Hashimoto M, Hossain S, Shimada T, Sugioka K, Yamasaki H, et al. 2002. Docosahexaenoic acid provides protection from impairment of learning ability in Alzheimer's disease model rats. J Neurochem 81: 1084–1091.
Hashimoto M, Tanabe Y, Fujii Y, Kikuta T, Shibata H, et al. 2005. Chronic administration of Docosahexaenoic acid ameliorates the impairment of spatial cognition learning ability amyloid beta-infused rats. Nutr Neurosci 135: 549–555.
Haubrich DR. 1973. Partial purification and properties of choline kinase (EC 22.214.171.124) from rabbit brain: Measurement of acetylcholine. J Neurochem 21: 315–328.
Haubrich DR, Gerber NH. 1981. Choline dehydrogenase. Assay, properties and inhibitors. Biochem Pharmacol 30: 2993–3000.
Haubrich DR, Gerber NH, Pflueger AB. 1979. Choline availability and the synthesis of acetylcholine. In: Nutrition and Brain, Vol. 5. Wurtman RJ, Wurtman JJ, editors. New York: Raven Press; pp. 57–71.
Haubrich DR, Wang PFL, Wedeking PW. 1975. Distribution and metabolism of intravenously administered choline [methyl-3H] and synthesis in vivo of acetylcholine in various tissues of guinea pigs. J Pharmacol Exp Ther 193: 246–255.
Haubrich DR, Wedeking PW, Wang PFL. 1974. Increase in tissue concentration of choline in guinea pigs in vivo induced by administration of choline. Life Sci 14: 921–927.
Henneberry AL, McMaster CR. 1999. Cloning and expression of a human choline/ethanolaminephosphotransferase: Synthesis of phosphatidylcholine and phosphatidylethanolamine. Biochem J 339: 291–298.
Henneberry AL, Wistow G, McMaster CR. 2000. Cloning, genomic organization, and characterization of a human cholinephosphotransferase. J Biol Chem 275: 29808–29815.
Hersh LB. 1982. Kinetic studies of the choline acetyltransferase reaction using isotope exchange at equilibrium. J Biol Chem 257: 12820–12834.
Hirata F, Axelrod J. 1978. Enzymatic synthesis and rapid translocation of phosphatidylcholine by two methyltransferases in erythrocyte membranes. Proc Natl Acad Sci USA 75: 2348–2352.
Hirata F, Viveros OH, Diliberto EJ Jr, Axelrod J. 1978. Identification and properties of two methyltransferases in conversion of phosphatidylethanolamine to phosphatidylcholine. Proc Natl Acad Sci USA 75: 1718–1721.
Hirsch MJ, Growdon JH, Wurtman RJ. 1978. Relations between dietary choline or lecithin intake, serum choline levels, and various metabolic indices. Metabolism 27: 953–960.
Hitzemann R. 1982. Developmental regulation of phospholipid methylation in rat brain synaptosomes. Life Sci 30: 1297–1303.
Hjelle JT, Welch MH, Pavlina TM, Webb LE, Mockler DF, et al. 1993. Choline levels in human peritoneal dialysate. Adv Perit Dial 9: 299–302.
Hogans AF, Guroff G, Udenfriend S. 1971. Studies on the origin of pyrimidines for biosynthesis of neural RNA in the rat. J Neurochem 18: 1699–1710.
Holbrook PG, Wurtman RJ. 1988. Presence of base-exchange activity in rat brain nerve endings: Dependence on soluble substrate concentrations and effect of cations. J Neurochem 50: 156–162.
Holler T, Cermak JM, Blusztajn JK. 1996. Dietary choline supplementation in pregnant rats increases hippocampal phospholipase D activity of the offspring. FASEB J 10: 1653–1659.
Holm PI, Ueland PM, Kvalheilm G, Lien EA. 2003. Determination of choline, betaine, and dimethylglycine in plasma by a high-throughput method based on normal-phase chromatography-tandem mass spectrometry. Clin Chem 49: 286–294.
Holmes GL, Yang Y, Liu Z, Cermak JM, Sarkisian MR, et al. 2002. Seizure-induced memory impairment is reduced by choline supplementation before or after status epilepticus. Epilepsy Res 48: 3–13.
Holmes HC, Snodgrass GJ, Iles RA. 2000. Changes in the choline content of human breast milk in the first 3 weeks after birth. Eur J Pediatr 159: 198–204.
Holmes-McNary MQ, Loy R, Mar MH, Albright CD, Zeisel SH. 1997. Apoptosis is induced by choline deficiency in fetal brain and in PC12 cells. Brain Res Dev Brain Res 101: 9–16.
Holz RW, Senter RA. 1981. Choline stimulates nicotinic receptors on adrenal medullary chromaffin cells to induce catecholamine secretion. Science 214: 466–468.
Houtsmuller UMT. 1979. Metabolic fate of dietary lecithin. In: Nutrition and Brain, Vol. 5. Wurtman RJ, Wurtman JJ, editors. New York: Raven Press; pp. 83–94.
Huang S, Lin Q. 2003. Functional expression and processing of rat choline dehydrogenase precursor. Biochem Biophys Res Commun 309: 344–350.
Huang X-P, Williams FE, Peseckis SM, Messer WS. 1998. Pharmacological characterization of human m1 muscarinic acetylcholine receptors with double mutations at the junction of TM VI and the third extracellular domain. J Pharmacol Exp Ther 286: 1129–1139.
Hung AY, Haass C, Nitsch RM, Qiu WQ, Citron M, et al. 1993. Activation of protein kinase C inhibits cellular production of the amyloid β-protein. J Biol Chem 268: 22959–22962.
Hurlbert RB, Kammen HO. 1960. Formation of cytidine nucleotides from uridine nucleotides by soluble mammalian enzymes: Requirements for glutamine and guanosine nucleotides. J Biol Chem 235: 443–449.
Hurwitz J. 1959. The enzymatic incorporation of ribonucleotides into polydeoxynucleotide material. J Biol Chem 234: 2351–2358.
Hutter F. 1952. Effect of choline on neuromuscular transmission in the cat. J Physiol (London) 117: 241–250.
Ilcol YO, Dilek K, Yurtkuran M. 2002a. Changes of plasma free choline and choline-containing compounds‘concentrations and choline loss during hemodialysis in ESRD patients. Clin Biochem 35: 307–313.
Ilcol YO, Uncu G, Ulus IH. 2002e. Free and phospholipid-bound choline concentrations in serum during pregnancy, after delivery and in newborns. Arch Physiol Biochem 110: 393–399.
Ilcol YO, Yilmaz Z, Ulus IH. 2003b. Serum free and phospholipid-bound choline decrease after surgery and methylprednisolone administration in dogs. Neurosci Lett 339: 195–198.
Ilcol YO, Yilmaz Z, Ulus IH. 2005b. Endotoxin alters serum free choline and phospholipid-bound choline concentrations, and choline administration attenuates endotoxin-induced organ injury in dogs. Shock 24: 288–293.
Ilcol YO, Basagan-Mogol E, Cengiz M, Ulus IH. 2006. Elevation of serum cerebral injury markers correlates with serum choline decline after coronary artery bypass grafting surgery. Clin Chem Lab Med 44: 471–478.
Ilcol YO, Gurun MS, Taga Y, Ulus IH. 2002c. Intraperitoneal administration of choline increases serum glucose in rat: Involvement of the sympathoadrenal system. Horm Metab Res 34: 341–347.
Ilcol YO, Gurun MS, Taga Y, Ulus IH. 2003a. Choline increases serum insulin in rat when injected intraperiotenally and augments basal and stimulated acetylcholine release from the rat minced pancreas in vitro. Eur J Biochem 270: 991–999.
Ilcol YO, Ozbek R, Hamurtekin E, Ulus IH. 2005a. Choline status in newborns, infants, children, breast-feeding women, breast-fed infants and human breast milk. J Nutr Biochem 16: 489–499.
Ilcol YO, Donmez O, Yavuz M, Dilek K, Yurtkuran M. 2002b. Free choline and phospholipid-bound choline concentrations in serum and dialysate during peritoneal dialysis in children and adults. Clin Biochem 35: 307–313.
Ilcol YO, Ozyurt G, Kilicturgay S, Uncu G, Ulus IH. 2002d. The decline in serum choline concentration in humans during and after surgery is associated with elevation of cortisol, adrenocorticotropic hormone, prolactin and β-endorphin concentrations. Neurosci Lett 324: 41–44.
Ilcol YO, Uncu G, Goren S, Sayan E, Ulus IH. 2004. Declines in serum free choline and bound choline concentrations in humans after three different types of major surgery. Clin Chem Lab Med 42: 1390–1395.
Illingworth DR, Portman OW. 1972. The uptake and metabolism of plasma lysophosphatidylcholine in vivo by the brain of squirrel monkeys. Biochem J 130: 557–567.
Inazu M, Takeda H, Matsumiya T. 2005. Molecular and functional characterization of an Na+-independent choline transporter in rat astrocytes. J Neurochem 94: 1427–1437.
Infante JP, Kinsella JE. 1978. Control of phosphatidylcholine synthesis and the regulatory role of choline kinase in rat liver. Evidence from essential-fatty acid-deficient rats. Biochem J 176: 631–633.
Institute of Medicine, National Academy of Science, USA. 1998. Choline. In: Dietary Reference Intakes for Folate, Thiamine, Riboflavin, Niacin, Vitamin B12, Panthothenic Acid, Biotin, and Choline, Washington DC: National Academy Press; pp. 390-422.
Isbil-Buyukcoskun N, Gulec G, Ozluk K, Ulus IH. 2001. Central injection of captopril inhibits the blood pressure response to intracerebroventricular choline. Braz J Med Biol Res 34: 815–820.
Ishidate K, Furusawa K-I, Nakazawa Y. 1985. Complete co-purification of choline kinase and ethanolamine kinase from rat kidney and immunological evidence for both kinase activities residing on the same enzyme protein(s) in rat tissues. Biochim Biophys Acta 836: 119–124.
Ishidate K, Matsuo R, Nakazawa Y. 1993. CDP-choline: 1,2-diacylglycerol cholinephosphotransferase from rat liver microsomes. I. Solubilization and characterization of the partially purified enzyme and the possible existence of an endogenous inhibitor. Lipids 28: 89–96.
Jackson DA, Kischka U, Wurtman RJ. 1995. Choline enhances scopolamine-induced acetylcholine release in dorsal hippocampus of conscious, freely-moving rats. Life Sci 56: 45–49.
Jamil H, Utal AK, Vance DE. 1992. Evidence that cyclic AMP-induced inhibition of phosphatidylcholine biosynthesis is caused by a decrease in cellular diacylglycerol levels in cultured rat hepatocytes. J Biol Chem 267: 1752–1760.
Jonnala RR, Graham III JH, Terry AV, Beach JW, Young JA, et al. 2003. Relative levels of cytoprotection produced by analogs of choline and the role of alpha7-nicotinic acetylcholine receptors. Synapse 47: 262–269.
Jope RS, Jenden DJ. 1981. Choline transport and the regulation of acetylcholine synthesis in synaptosomes. In: Cholinergic Mechanisms: Phylogenetic Aspects, Central and Peripheral Synapses, and Clinical Significance, Pepeu G, Ladinsky L, editors. New York: Plenum Press; pp. 497–510.
Jope RS, Wright SM, Jenden DJ. 1984. Choline flux in human erythrocytes. Psychopharmacol Bull 20: 674–680.
Jope RS, Tolbert LC, Wright SM, Walter-Ryan W. 1985a. Biochemical RBC abnormalities in drug-free and lithium-treated manic patients. Am J Psychiatry 142: 356–358.
Jope RS, Walter-Ryan W, Alarcon RD, Lally KM. 1985b. Cholinergic processes in blood samples from patients with major psychiatric disorders. Biol Psychiatry 20: 1258–1266.
Jope RS, Wright SM, Walter-Ryan W, Alarcon RD. 1986. Effects of bipolar affective disorder and lithium administration on the cholinergic system in human blood. J Psychiatr Res 20: 9–19.
Jope RS, Jenden DJ, Erlich BE, Diamond JM, Gosenfeld LF. 1980. Erythrocyte choline concentrations are elevated in manic patients. Proc Natl Acad Sci USA 77: 6144–6146.
Kakihana M, Fukuda N, Suno M, Nagaoka A. 1988. Effects of CDP-choline on neurologic deficits and cerebral glucose metabolism in a rat model of cerebral ischemia. Stroke 19: 217–222.
Kalmar GB, Kay RJ, Lachance A, Cornell RB. 1994. Primary structure and expression of a human CTP: Phosphocholine cytidylyltransferase. Biochim Biophys Acta 1219: 328–334.
Kalmar GB, Kay RJ, Lachance A, Aebersold R, Cornell RB. 1990. Cloning and expression of rat liver CTP: Phosphocholine cytidylyltransferase: An amphipathic protein that controls phosphatidylcholine synthesis. Proc Natl Acad Sci USA 87: 6029–6033.
Kano H, Ohno K. 1973a. Utilization of endogenous phospholipids by the backreaction of CDP-choline (-ethanolamine): 1,2-diglyceride choline (ethanolamine)-phosphotransferase in rat liver microsomes. Biochim Biophys Acta 306: 207–217.
Kano H, Ohno K. 1973b. Studies on 1,2-diglycerides formed from endogenous lecithins by the back-reaction of rat liver microsomal CDPcholine: 1,2-diacylglycerol cholinephosphotransferase. Biochim Biophys Acta 326: 17–25.
Kanof PD, Greenwald BS, Mohs RC, Davis KL. 1985. Red blood cell choline. II: Kinetics in Alzheimer's disease. Biol Psychiatry 20: 375–383.
Kanoh H, Ohno K. 1976. Solubilization and purification of rat liver microsomal 1,2-diacylglycerol: CDP-choline cholinephosphotransferase and 1,2-diacylglycerol: CDP-ethanolamine ethanolaminephosphotransferase. Eur J Biochem 66: 201–210.
Kapp J, Mahaley MS, Odom GL. 1970. Experimental evaluation of potential spasmalytic drugs. J Neurosurg 32: 468–472.
Karim M, Jackson P, Jackowski S. 2003. Gene structure, expression and identification of a new CTP: Phosphocholine cytidylyltransferase beta isoform. Biochim Biophys Acta 1633: 1–12.
Kekuda R, Prasad PD, Wu X, Wang H, Fei Y-J, et al. 1998. Cloning and functional characterization of a potential-sensitive, polyspecific organic cation transporter (OCT3) most abundantly expressed in placenta. J Biol Chem 273: 15971–15979.
Kennedy EP, Weiss SB. 1956. The function of cytidine coenzymes in the biosynthesis of phospholipides. J Biol Chem 222: 193–214.
Kessler PD, Marchbanks RM. 1979. Choline transport is not coupled to acetylcholine synthesis. Nature 279: 542–544.
Kharbanda KK, Rogers DD, Mailliard ME, Siford GL, Barak AJ, et al. 2005. Role of elevated S-adenosylhomocysteine in rat hepatocyte apoptosis: Protection by betaine. Biochem Pharmacol 70: 1883–1890.
Kilbinger H, Kruel R. 1981. Choline inhibits acetylcholine release via presynaptic muscarine receptors. Naunyn Schmiedebergs Arch Pharmacol 316: 131–134.
Kim SH, Fountoulakis M, Cairns NJ, Lubec G. 2002. Human brain nucleoside diphosphate kinase activity is decreased in Alzheimer's disease and Down syndrome. Biochem Biophys Res Commun 296: 970–975.
Klee WA, Richards HH, Cantoni GL. 1961. The synthesis of methionine by enzymic transmethylation. VII. Existence of two separate homocysteine methylpherases on mammalian liver. Biochim Biophys Acta 54: 157–164.
Klein J, Koppen A, Loffelholz K. 1990. Small rises in plasma choline reverse the negative arteriovenous difference of brain choline. J Neurochem 55: 1231–1236.
Klein J, Koppen A, Loffelholz K. 1998. Regulation of free choline in rat brain: Dietary and pharmacological manipulations. Neurochem Int 32: 479–485.
Klein J, Gonzales R, Koppen A, Loffelholz K. 1993. Free choline and choline metabolites in rat brain and body fluids: Sensitive determination and implications for choline supply to the brain. Neurochem Int 22: 293–300.
Koehler MR, Wissinger B, Gorboulev V, Koepsell H, Schmid M. 1997. The two human organic cation transporter genes SLC22A1 and SLC22A2 are located on chromosome 6q26. Cytogenet Cell Genet 79: 198–200.
Koepsell H, Endou H. 2004. The SLC22 drug transporter family. Pflugers Arch 447: 666–676.
Koepsell H, Schmitt BM, Gorboulev V. 2003. Organic cation transporters. Rev Physiol Biochem Pharmacol 150: 36–90.
Koizumi K, Shimamoto Y, Azuma A, Wataya Y, Matsuda A, et al. 2001. Cloning and expression of uridine/cytidine kinase cDNA from human fibrosarcoma cells. Int J Mol Med 8: 273–278.
Kopf SR, Bucholzer ML, Hilgert M, Loffelholz K, Klein J. 2001. Glucose plus choline improve passive avoidance behaviour and increase hippocampal acetylcholine release. Neuroscience 103: 365–371.
Korniat EK, Beeler DA. 1975. Water-soluble phospholipid precursor pool-sizes in quick-frozen and unfrozen rat livers. Anal Biochem 69: 300–305.
Kosterlitz HW, Lees GM, Wallis DI. 1968. Resting and action potentials recorded by the sucrose-gap method in the superior cervical ganglion of the rabbit. J Physiol (London) 195: 39–53.
Krnjevic K, Reinhardt W. 1979. Choline excites cortical neurons. Science 205: 1321–1322.
Krstic MK. 1972. The action of choline on the superior cervical ganglion of the cat. Eur J Pharmacol 17: 87–96.
Krystal G, Webb TE. 1971. Multiple forms of uridine kinase in normal and neoplastic rat liver. Biochem J 124: 943–947.
Kubo T, Misu Y. 1981a. Blood pressure response to intracisternal administration of choline. Jpn J Pharmacol 31: 839–841.
Kubo T, Misu Y. 1981b. Cardiovascular response to microinjection of physostigmine and choline into the dorsal medullary site of the rat. Neuropharmacology 20: 1091–1095.
Kuchel PW, Hunt GE, Johnson GF, Beilharz GR, Chapman BE, et al. 1984. Lithium, red blood cell choline and clinical state. A prospective study in manic depressive patients. J Affect Disord 6: 83–94.
Kuhar MJ, Murrin LC. 1978. Sodium-dependent high-affinity choline uptake. J Neurochem 30: 15–21.
Kuntscherova J. 1972. Effect of short-term starvation and choline on the acetylcholine content of organs of albino rats. Physiol Bohemoslov 21: 655–660.
Kus L, Borys E, Chu YP, Ferguson SM, Blakely RD, et al. 2003. Distribution of high affinity choline transporter immunoreactivity in the primate central nervous system. J Comp Neurol 436: 341–357.
Ladd SL, Sommer SA, La Berge S, Toscana W. 1993. Effect of phosphatidylcholine on explicit memory. Clin Neuropharmacol 16: 540–549.
Langen H, Berndt P, Roder D, Cairns N, Lubec G, et al. 1999. Two dimensional map of human brain proteins. Electrophoresis 20: 907–916.
Larrayoz IM, Fernandez-Nistal A, Garces A, Gorraitz E, Lostao MP. 2006. Characterization of the rat Na +/nucleoside cotransporter 2 (rCNT2) and transport of nucleoside-derived drugs using electrophysiological methods. Am J Physiol Cell Physiol 291: 1395-1404.
Leathwood PD, Heck E, Mauron J. 1982. Phosphatidylcholine and avoidance performance in 17 month old SEC/1ReJ mice. Life Sci 30: 1065–1070.
Lee C, Hajra AK. 1991. Molecular species of diacylglycerols and phosphoglycerides and the postmortem changes in the molecular species of diacylglycerols in rat brains. J Neurochem 56: 370–379.
Li JY, Boado RJ, Pardridge WM. 2001. Cloned blood–brain barrier adenosine transporter is identical to the rat concentrative Na+ nucleoside cotransporter CNT2. J Cereb Blood Flow Metab 21: 929–936.
Li Q, Guo-Ross S, Lewis DV, Turner D, White AM, et al. 2003. Dietary prenatal choline supplementation alters postnatal hippocampal structure and function. J Neurophysiol 91: 1545–1555.
Li XD, Buccafusco JJ. 2004. Role of α7 nicotinic acetylcholine receptors in the pressor response to intracerebroventricular injection of choline: Blockade by amyloid peptide Aβ1–42. J Pharmacol Exp Ther 309: 1206–1212.
Lieberman I. 1956. Enzymatic amination of uridine triphosphate to cytidine triphosphate. J Biol Chem 222: 765–775.
Lim P, Cornell R, Vance DE. 1986. The supply of both CDP-choline and diacylglycerol can regulate the rate of phosphatidylcholine synthesis in HeLa cells. Biochem Cell Biol 64: 692–698.
Lin CS, Wu RD. 1986. Choline oxidation and choline dehydrogenase. J Protein Chem 5: 193–200.
Lips KS, Pfeil U, Haberberger RV, Kummer W. 2002. Localisation of the high-affinity choline transporter in the rat motor skeletal unit. Cell Tissue Res 307: 275–280.
Lips KS, Pfeil U, Reiners K, Rimasch C, Kuchelmeister K, et al. 2003. Expression of the high-affinity choline transporter CHT1 in rat and human arteries. J Histochem Cytochem 51: 1645–1654.
Lopez G-Coviella I, Wurtman RJ. 1992. Enhancement by cytidine of membrane phospholipid synthesis. J Neurochem 59: 338–343.
Lopez G-Coviella, I, Agut J, Wurtman RJ. 1986. Effect of cytidine (5′)diphosphocholine (CDP-choline) on the total urinary excretion of 3-methoxy-4-hydroxyphenylglycol (MHPG) by rats and humans. J Neural Transm 66: 129–134.
Lopez G-Coviella I, Agut J, Wurtman RJ. 1987. Metabolism of cytidine (5′)-diphosphocholine (CDP-choline) following oral and intravenous administration to the human and the rat. Neurochem Int 11: 293–297.
Lopez G-Coviella I, Agut J, Ortiz JA, Wurtman RJ. 1992. Effects of orally administered cytidine 5′-diphosphate choline on brain phospholipid content. J Nutr Biochem 3: 313–315.
Lopez G-Coviella I, Agut J, Savci V, Ortiz JA, Wurtman RJ. 1995. Evidence that 5′-Cytidinediphosphocholine can affect brain phospholipid composition by increasing choline and cytidine plasma levels. J Neurochem 65: 889–894.
Lopez G-Coviella I, Clark WM, Warach S, Sandage B, Agut J, et al. 1998. CDP-Choline (Citicoline): Potential mechanisms of action and preliminary results in human stroke. In: Restorative Neurology: Advances in Pharmacotherapy for Recovery after Stroke, Goldstein LB, editor. Armonk, New York: Futura Publishing Co., Inc.; pp. 195–212.
Loy R, Heyer DD, Williams CL, Meck WH. 1991. Choline-induced spatial memory facilitation correlates with altered distribution and morphology of septal neurons. Adv Exp Med Biol 295: 373–382.
Lykidis A, Baburina I, Jackowski S. 1999. Distribution of CTP: Phosphocholine cytidylyltransferase (CCT) isoforms. Identification of a new CCTbeta splice variant. J Biol Chem 274: 26992–27001.
Lykidis A, Murti KG, Jackowski S. 1998. Cloning and characterization of a second human CTP: Phosphocholine cytidylyltransferase. J Biol Chem 273: 14022–14029.
Lykidis A, Wang J, Karim MA, Jackowski S. 2001. Overexpression of a mammalian ethanolamine-specific kinase accelerates the CDP-ethanolamine pathway. J Biol Chem 276: 2174–2179.
MacIntosh FC. 1979. Are acetylcholine levels related to acetylcholine release? In: Nutrition and the Brain, Vol. 5. Barbeau A, Growdon JH, Wurtman RJ, editors. New York: Raven Press; pp. 201–217.
Mages F, Rey C, Fonlupt P, Pacheco H. 1988. Kinetic and biochemical properties of CTP: Choline-phosphate cytidylyltransferase from the rat brain. Eur J Biochem 178: 367–372.
Magil SG, Zeisel SH, Wurtman RJ. 1981. Effects of ingesting soy or egg lecithins on serum choline, brain choline and brain acetylcholine. J Nutr 111: 166–170.
Maire J-C, Wurtman RJ. 1985. Effects of electrical stimulation and choline availability on the release and contents of acetylcholine and choline in superfused slices from rat striatum. J Physiol 80: 189–195.
Manabe F, Tsutsumi A, Yamamoto Y, Hashimoto Y, Ishizu H. 1991. The identification of human semen by a chemiluminescent assay of choline. Nihon Hoigaku Zasshi 45: 205–215.
Mandel P, Edel-Harth S. 1966. Free nucleotides in the rat brain during post-natal development. J Neurochem 13: 591–595.
Mandelzys A, De Koninck P, Cooper E. 1995. Agonist and toxin sensitivities of ACh-evoked currents on neurons expressing multiple nicotinic subunits. J Neurophysiol 74: 1212–1221.
Mann PJG, Quastel JH. 1937. The oxidation of choline by rat liver. Biochem J 31: 869–878.
Mantel CR, Schultz AR, Miyazawa K, Broxmeyer HE. 1993. Kinetic selectivity of cholinephosphotransferase in mouse liver: The K m for CDP-choline depends on diacylglycerol structure. Biochem J 289: 815–820.
Marshall DL, De Mitcheli E, Bogdanov MB, Wurtman RJ. 1996. Effects of ethanolamine (Etn) administration on Etn and choline (Ch) levels in plasma, brain extracellular fluid (ECF) and brain tissue, and on brain phospholipid levels in rats: An in vivo study. Neurosci Res Commun 18: 87–96.
Marszalek JR, Lodish HF. 2005. Docosahexaenoic acid, fatty acid-interacting proteins, and neuronal function: Breastmilk and fish are good for you. Annu Rev Cell Dev Biol 21: 633–657.
Marszalek JR, Kitidis C, Di Russo CC, Lodish HF. 2005. Long-chain acyl-CoA synthetase 6 preferentially promotes DHA metabolism. J Biol Chem 280: 10817–10826.
Martinez M. 1992. Abnormal profiles of polyunsaturated fatty acids in the brain, liver, kidney and retina of patients with peroxisomal disorders. Brain Res 583: 171–182.
Martinet M, Fonlupt P, Pacheco H. 1979. Effects of cytidine-5′ diphosphocholine on norepinephrine, dopamine and serotonin synthesis in various regions of the rat brain. Arch Int Pharmacodyn Ther 239: 52–60.
Martinet M, Fonlupt P, Pacheco H. 1981. Activation of soluble striatal tyrosine hydroxylase in the rat brain after CDP choline administration. Biochem Pharmacol 30: 539–541.
Marzloff G, Cansev M, Wurtman RJ. 2006. Uridine plus docosahexaenoic acid supplementation in rat dams during gestation and nursing markedly increases brain phospholipids in their pups. Society for Neuroscience Abstracts, Atlanta, Georgia, 14–18 October.
Mascia L, Cotrufo T, Cappiello M, Ipata PL. 1999. Ribose 1-phosphate and inosine activate uracil salvage in rat brain. Biochim Biophys Acta 1472: 93–98.
Matthews EK. 1966. The presynaptic effects of quaternary ammonium compounds on the release of acetylcholine from the stimulated perfused superior cervical ganglion of the cat. Br J Pharmacol 26: 552–556.
Meck WM, Williams CL. 1997a. Perinatal choline supplementation increases the threshold for chunking in spatial memory. Neuroreport 8: 3053–3059.
Meck WM, Williams CL. 1997b. Simultaneous temporal processing is sensitive to prenatal choline availability in mature and aged rats. Neuroreport 8: 3045–3051.
Meck WM, Williams CL. 1997c. Characterization of the facilitative effects of perinatal choline supplementation on timing and temporal memory. Neuroreport 8: 2831–2835.
Meck WM, Williams CL. 1999. Choline supplementation during prenatal development reduces proactive interference in spatial memory. Brain Res Dev Brain Res 118: 51–59.
Meck WM, Smith RA, Williams CL. 1988. Pre- and postnatal choline supplementation produces long-term facilitation of spatial memory. Dev Psychobiol 21: 339–353.
Meck WM, Smith RA, Williams CL. 1989. Organizational changes in cholinergic activity and enhanced visuospatial memory as a function of choline administered prenatally or postnatally or both. Behav Neurosci 103: 1234–1241.
Mellott TJ, Williams C, Meck WH, Blusztajn JK. 2004. Prenatal choline supplementation advances hippocampal development and enhances MAPK and CREB activation. FASEB J 18: 545–557.
Mendel LB, Underhill FP, Renshaw RR. 1912. The action of salts of choline on arterial blood pressure. J Pharmacol Exp Ther 3: 649–660.
Mervis RF. 1982. Chronic dietary choline represses age-related loss of dentritic spines in mouse neocortical pyramidal cells. J Neuropathol Exp Neurol 41: 363
Meyer EM, Baker SP. 1986. Effects of choline augmentation on acetylcholine release in rat atrial minces. Life Sci 39: 1307–1315.
Miller LG, Greenblatt DJ, Roy RB, Lopez F, Wecker L. 1989. Dietary choline intake modulates benzodiazepine receptor binding and γ-aminobutyric acid A receptor function in mouse brain. J Pharmacol Exp Ther 248: 1–6.
Millington WR, Wurtman RJ. 1982. Choline administration elevates brain phosphorylcholine concentrations. J Neurochem 38: 1748–1752.
Millington WR, McCall AL, Wurtman RJ. 1978. Deanol acetamidobenzoate inhibits the blood–brain barrier transport of choline. Ann Neurol 4: 302–306.
Mir C, Clotet J, Aledo R, Durany N, Argemi J, et al. 2003. CDP-choline prevents glutamate-mediated cell death in cerebellar granule neurons. J Mol Neurosci 20: 53–60.
Misawa H, Ishi K, Deguchi T. 1992. Gene expression of mouse choline acetyltransferase: Alternative splicing and identification of a highly active promoter region. J Biol Chem 267: 20392–20399.
Misawa H, Matsuura J, Oda Y, Takahashi R, Deguchi T. 1997. Human choline acetyltransferase mRNAs with different 5′-region produce a 69-kD major translation product. Mol Brain Res 44: 323–333.
Misawa H, Nakata K, Matsuura J, Nagao M, Okuda T, et al. 2001. Distribution of the high-affinity choline transporter in the central nervous system of the rat. Neuroscience 105: 87–98.
Montoya D, Swartzwelder HS. 2000. Prenatal choline supplementation alters hippocampal N-methyl-D-aspartate receptor-mediated neurotransmission in adult rats. Neurosci Lett 296: 85–88.
Montoya DA, White AM, Williams CL, Blusztajn JK, Meck WH, et al. 2000. Prenatal choline exposure alters hippocampal responsiveness to cholinergic stimulation in adulthood. Brain Res 123: 25–32.
Mooradian AD. 1988. Blood–brain barrier transport of choline is reduced in the aged rat. Brain Res 440: 328–332.
Mooslehner KA, Allen ND. 1999. Cloning of the mouse organic cation transporter 2 gene, Slc22a2, from an enhancer-trap transgene integration locus. Mamm Genome 10: 218–224.
Morley BJ, Garner LL. 1986. Increases in the concentration of brain alpha-bungarotoxin binding sites induced by dietary choline are age dependent. Brain Res 378: 315–319.
Mozzi R, Porcellati G. 1979. Conversion of phosphatidylethanolamine to phosphatidylcholine in rat brain by the methylation pathway. FEBS Lett 100: 363–366.
Mulholland PJ, Self RL, Harris BR, Littleton JM, Prendergast MA. 2004. Choline exposure reduces potentiation of N-methyl-D-aspartate toxicity by corticosterone in the developing hippocampus. Brain Res Dev Brain Res 153: 203–211.
Murakami H, Ohkura A, Takanaga H, Matsuo H, Koyabu N, et al. 2005. Functional characterization of adenosine transport across the BBB in mice. Int J Pharm 290: 37–44.
Nagai K, Nagasawa K, Koma M, Hotta A, Fujimoto S. 2006a. Cytidine is a novel substrate for wild-type concentrative nucleoside transporter 2. Biochem Biophys Res Commun 347: 439–443.
Nagai K, Nagasawa K, Koma M, Kihara Y, Fujimoto S. 2006b. Contribution of an unidentified sodium-dependent nucleoside transport system to the uptake and cytotoxicity of anthracycline in mouse M5076 ovarian sarcoma cells. Biochem Pharmacol 71: 565–573.
Nakata K, Okuda T, Misawa H. 2004. Ultrastructural localization of high-affinity choline transporter in the rat neuromuscular junction: Enrichment on synaptic vesicles. Synapse 53: 53–56.
Neill AR, Grime DW, Dawson RMC. 1978. Conversion of choline methyl groups through trimethylamine into methane in the rumen. Biochem J 170: 529–535.
Nitsch RM, Wurtman RJ, Growdon JH. 1994. Regulation of APP processing by first messengers. In: Alzheimer's Disease: Therapeutic Strategies, Giacobini E, Becker R, editors. Boston: Burkhauser; pp. 54–61.
Nitsch RM, Blusztajn JK, Pittas AG, Slack BE, Growdon JH, et al. 1992. Evidence for a membrane defect in Alzheimer disease brain. Proc Natl Acad Sci USA 89: 1671–1675.
O K-M, Choy PC. 1990. Solubilization and partial purification of cholinephosphotransferase in hamster tissues. Lipids 25: 122–124.
Oda Y. 1999. Choline acetyltransferase: The structure, distribution and pathologic changes in the central nervous system. Pathol Int 49: 921–937.
Oda Y, Nakanishi I, Deguchi T. 1992. A complementary DNA for human choline acetyltransferase induces two forms of enzyme with different molecular weights in cultured cells. Mol Brain Res 16: 287–294.
Okuda M, Saito H, Urakami Y, Takano M, Inui K. 1996. cDNA cloning and functional expression of a novel rat kidney organic cation transporter, OCT2. Biochem Biophys Res Commun 224: 500–507.
Okuda T, Haga T. 2003. High-affinity choline transporter. Neurochem Res 28: 483–488.
Okuda T, Haga T, Kanai Y, Endou H, Ishihara T, et al. 2000. Identification and characterization of the high-affinity choline transporter. Nat Neurosci 3: 120–125.
Oldendorf WH, Braun LD. 1976. [H]Tryptamine and 3H-water as diffusible internal standards for measuring brain extraction of radio-labeled substances following carotid injection. Brain Res 113: 219–224.
Onal MZ, Li F, Tatlisumak T, Locke KW, Sandage BW, et al. 1997. Synergistic effects of citicoline and Mk-801 in temporary experimental focal ischemia in rats. Stroke 28: 1060–1065.
O'Regan S, Collier B. 1981. Effect of increasing choline, in vivo and in vitro, on the synthesis of acetylcholine in a sympathetic ganglion. J Neurochem 36: 420–430.
O'Regan S, Traiffort E, Ruat M, Cha N, Compaore D, et al. 2000. An electric lobe suppressor for a yeast choline transport mutation belongs to a new family of transporter-like proteins. Proc Natl Acad Sci USA 97: 1835–1840.
Ordonez LA, Wurtman RJ. 1974. Folic acid deficiency and methyl group metabolism in rat brain: Effects of L-Dopa. Arch Biochem Biophys 160: 372–376.
Orengo A. 1969. Regulation of enzymic activity by metabolites. I. Uridine-cytidine kinase of Novikoff ascites rat tumor. J Biol Chem 244: 2204–2209.
Oshitari T, Fujimoto N, Adachi-Usami E. 2002. Citicoline has a protective effect on damaged retinal ganglion cells in mouse culture retina. Neuroreport 13: 2109–2111.
Pahud G, Medilanski J, Eder-Colli L. 2003. Cytosolic choline acetyltransferase binds specifically to cholinergic plasma membrane of rat brain synaptosomes to generate membrane-bound enzyme. Neurochem Res 28: 543–549.
Pahud G, Salem N, Van de Goor J, Medilanski J, Pellegrinelli N, et al. 1998. Study of subcellular localization of membrane-bound choline acetyltransferase in Drosophila central nervous system and its association with membranes. Eur J Neurosci 10: 1644–1653.
Palacios JM, Kuhar MJ. 1979. Choline: Binding studies provide some evidence for a weak, direct agonist action in brain. Mol Pharmacol 16: 1084–1088.
Papke RL, Papke JKP. 2002. Comparative pharmacology of rat and human alpha7 nAChR conducted with net charge analysis. Br J Pharmacol 137: 49–61.
Papke RL, Bencherif M, Lippiello P. 1996. An evaluation of neuronal nicotinic acetylcholine receptor activation by quaternary nitrogen compounds indicates that choline is selective for the alpha7 subtype. Neurosci Lett 213: 201–204.
Papke RL, Meyer E, Nutter T, Uteshev VV. 2000. Alpha7 receptor-selective agonists and modes of alpha7 receptor activation. Eur J Pharmacol 393: 179–195.
Pardridge WM. 1986. Blood–brain barrier transport of nutrients. Introduction. Fed Proc 45: 2047–2049.
Pardridge WM. 2001. Invasive brain drug delivery. In: Brain Drug Targeting: The Future of Brain Drug Development. Pardridge WM, editor. Cambridge, UK: Cambridge University Press; pp. 13–35.
Pardridge WM, Oldendorf WH. 1977. Transport of metabolic substrates through the blood–brain barrier. J Neurochem 28: 5–12.
Pardridge WM, Cornford EM, Braun LD, Oldendorf WH. 1979. Transport of choline and choline analogues through the blood–brain barrier. In: Nutrition and the Brain, Vol. 5. Barbeau MD, Growdon JH, Wurtman RJ, editors. New York: Raven Press; pp. 25–34.
Parducz A, Joo F, Toldi J. 1986. Formation of synaptic vesicles in the superior cervical ganglion of cat: Choline dependency. Exp Brain Res 63: 221–224.
Parducz A, Kiss Z, Joq F. 1976. Changes of the phosphatidylcholine content and the number of synaptic vesicles in relation to the neurohumoral transmission in sympathetic ganglia. Experientia 32: 1520–1521.
Parks RE Jr, Agarwal RP. 1973. Nucleoside diphosphokinases. In: The Enzymes. Boyer PD, editor. New York: Academic Press; pp. 307–333.
Pastor-Anglada M, Felipe A, Casado FJ. 1998. Transport and mode of action of nucleoside derivatives used in chemical and antiviral therapies. Trends Pharmacol Sci 19: 424–430.
Pelech SL, Cook HW, Paddon HB, Vance DE. 1984. Membrane-bound CTP: Phosphocholine cytidylyltransferase regulates the rate of phosphatidylcholine synthesis in HeLa cells treated with unsaturated fatty acids. Biochim Biophys Acta 795: 433–440.
Percy AK, Moore JF, Waechter CJ. 1982. Properties of particulate and detergent-solubilized phospholipid N-methyltransferase activity from calf brain. J Neurochem 38: 1404–1412.
Peters GJ, van Groeningen CJ, Laurensse EJ, Lankelma J, Leyva A, et al. 1987. Uridine-induced hypothermia in mice and rats in relation to plasma and tissue levels of uridine and its metabolites. Cancer Chemother Pharmacol 20: 101–108.
Petkov VD, Kehayov RA, Mosharrof AH, Petkov VV, Getova D, et al. 1993. Effects of cytidine diphosphate choline on rats with memory deficits. Arzneimittelforschung 43: 822–828.
Petkov VD, Mosharrof AH, Kehayov R, Petkov VV, Kostantinova E, et al. 1992. Effects of CDP-choline on learning and memory processes in rodents. Methods Find Exp Clin Pharmacol 14: 593–605.
Pfeil U, Haberberger RV, Lips KS, Eberling L, Grau V, et al. 2003. Expression of the high-affinity choline transporter CHT1 in epithelia. Life Sci 72: 2087–2090.
Pietruszko R, Chern M-K. 2001. Betaine aldehyde dehydrogenase from rat liver mitochondrial matrix. Chem Biol Interact 130–132: 193–199.
Pinsky C, Frederickson RCA, Vazquez AJ. 1973. Morphine withdrawal syndrome responses to cholinergic antagonists an to a partial cholinergic agonist. Nature 242: 59–60.
Pomeroy AR, Raper C. 1972. Cholinomimetic activity of dimethylamino-ethanol, and -propanol and related compounds. Eur J Pharmacol 17: 81–86.
Pooler AM, Guez DH, Benedictus R, Wurtman RJ. 2005. Uridine enhances neurite outgrowth in nerve growth factor-differentiated pheochromocytoma cells. Neuroscience 134: 207–214.
Porter TJ, Kent C. 1990. Purification and characterization of choline/ethanolamine kinase from rat liver. J Biol Chem 265: 414–422.
Pyapali GK, Turner DA, Williams CL, Meck WH, Swartwelder HS. 1998. Prenatal dietary choline supplementation decreases the threshold for induction of long-term potentiation in young adult rats. J Neurophysiol 79: 1790–1796.
Ragozzino ME, Gold PE. 1995. Glucose injections into the medial septum reverse the effects of intraseptal morphine infusions on hippocampal acetylcholine output and memory. Neuroscience 68: 981–988.
Ragozzino ME, Arankowsky-Sandoval G, Gold PE. 1994. Glucose attenuates the effect of combined muscarinic-nicotinic receptor blockade on spontaneous alternation. Eur J Pharmacol 256: 31–36.
Ragozzino ME, Unick KE, Gold PE. 1996. Hippocampal acetylcholine release during memory testing in rats: Augmentation by glucose. Proc Natl Acad Sci USA 93: 4693–4698.
Ragozzino ME, Pal SN, Unick KE, Stefani MR, Gold PE. 1998. Modulation of hippocampal acetylcholine release and spontaneous alternation scores by intrahippocampal glucose injections. J Neurosci 18: 1595–1601.
Rao AM, Hatcher JF, Dempsey RJ. 1999. CDP-choline: Neuroprotection in transient forebrain ischemia of gerbils. J Neurosci Res 58: 697–705.
Rao AM, Hatcher JF, Dempsey RJ. 2000. Lipid alterations in transient forebrain ischemia: Possible new mechanisms of CDP-choline neuroprotection. J Neurochem 75: 2528–2535.
Reddy TJ, Sprecher H, Bazan NG. 1984. Long-chain acyl-CoA synthetase from rat brain microsomes. Kinetic studies using [1–14C] docosahexaenoic acid substrate. Eur J Biochem 145: 21–29.
Redzic ZB, Biringer J, Barnes K, Baldwin SA, Al-Sarraf H, et al. 2005. Polarized distribution of nucleoside transporters in rat brain endothelial and choroid plexus epithelial cells. J Neurochem 94: 1420–1426.
Rehman HU. 1999. Fish odour syndrome. Postgrad Med J 75: 451–452.
Reinhardt RR, Wecker L. 1983. Evidence for membrane-associated choline kinase activity in rat striatum. J Neurochem 41: 623–629.
Rendina G, Singer TP. 1959. Studies on choline dehydrogenase. I. Extraction in soluble form, assay, and some properties of the enzyme. J Biol Chem 234: 1605–1610.
Rennick B, Acara M, Hysert P, Mookerjee B. 1976. Choline loss during hemodialysis: Homeostatic control of plasma choline concentrations. Kidney Int 10: 329–335.
Renshaw PF, Daniels S, Lundahl LH, Rogers V, Lukas SE. 1999. Short-term treatment with citicoline (CDP-choline) attenuates some measures of craving in cocaine-dependent subjects: A preliminary report. Psychopharmacology 142: 132–138.
Ribeiro FM, Alves-Silva J, Volknandt W, Martins-Silva C, Mahmud H, et al. 2003. The hemicholinium-3 sensitive high affinity choline transporter is internalized by clathrin-mediated endocytosis and is present in endosomes and synaptic vesicles. J Neurochem 87: 136–146.
Ribeiro FM, Black SA, Prado VF, Rylett RJ, Ferguson SS, et al. 2005. Constitutive high-affinity choline transporter endocytosis is determined by a carboxyl-terminal tail dileucine motif. J Neurochem 94: 86–96.
Richardson UI, Wurtman RJ. 2006. Polyunsaturated fatty acids regulate phosphatidylcholine synthesis in PC12 cells. Lipids (submitted).
Richardson UI, Watkins CJ, Pierre C, Ulus IH, Wurtman RJ. 2003. Stimulation of CDP-choline synthesis by uridine or cytidine in PC12 rat pheochromocytoma cells. Brain Res 971: 161–167.
Ricny J, Tucek S, Novakova J. 1992. Acetylcarnitine, carnitine and glucose diminish the effect of muscarinic antagonist quinuclidinyl benzilate on striatal acetylcholine content. Brain Res 576: 215–219.
Riley SP, Talbot MJ, Jouhal AK, Hendry BM. 1997. Characterization of human erythrocyte choline transport in chronic renal failure. Nephrol Dial Transplant 12: 1921–1927.
Rivera CA, Wheeler MD, Enomoto N, Thurman RG. 1998. A choline-rich diet improves survival in a rat model of endotoxic shock. Am J Physiol 275: G862–G867.
Robert I, Quirin-Stricker C. 2001. A novel untranslated ‘exon H’ of the human choline acetyltransferase gene in placenta. J Neurochem 79: 9–16.
Roberti R, Mancini A, Freysz L, Binaglia L. 1992. Reversibility of the reactions catalyzed by cholinephosphotransferase and ethanolaminephosphotransferase solubilized from rat-brain microsomes. Biochim Biophys Acta 1165: 183–188.
Roberti R, Vecchini A, Freysz L, Masoom M, Binaglia L. 1989. An improved procedure for the purification of ethanolaminephosphotransferase. Reconstitution of the purified enzyme with lipids. Biochim Biophys Acta 1004: 80–88.
Ropp PA, Traut TW. 1996. Cloning and expression of a cDNA encoding uridine kinase from mouse brain. Arch Biochem Biophys 336: 105–112.
Ropp PA, Traut TW. 1998. Uridine kinase: Altered enzyme with decreased affinities for uridine and CTP. Arch Biochem Biophys 359: 63–68.
Rosenberger TA, Villacreses NE, Hovda JT, Bosetti F, Weerasinghe G, et al. 2004. Rat brain arachidonic acid metabolism is increased by a 6-day intracerebral ventricular infusion of bacterial lipopolysaccharide. J Neurochem 88: 1168–1178.
Ross BM, Moszczynska A, Blusztajn JK, Sherwin A, Lozano A, et al. 1997. Phospholipid biosynthetic enzymes in human brain. Lipids 32: 351–358.
Rossier J. 1977. Acetyl-coenzyme A and coenzyme A analogues. Their effects on rat brain choline acetyltransferase. Biochem J 165: 321–326.
Rothschild HA, Cori O, Baron ESG. 1954. The components of choline oxidase and aerobic phosphorylation coupled with choline oxidation. J Biol Chem 208: 41–53.
Ruffner BW, Anderson EP. 1969. Adenosine triphosphate: Uridine monophosphate-cytidine monophosphate phosphotransferase from Tetrahymena pyriformis. J Biol Chem 244: 5994–6002.
Rylett RJ, Walters SA, Davis W. 1996. Identification and partial characterization of the high-affinity choline carrier from rat brain striatum. Brain Res Mol Brain Res 35: 354–358.
Sakamoto T, Wurtman RJ. 2006. Nutritional supplementation with uridine-5′-monophosphate and docosahexaenoic acid increases dendritic spine density in developing rats. Society for Neuroscience Abstracts, Atlanta, Georgia, 14–18 October.
Salem N, Medilanski J, Pellegrinelli N, Eder-Colli L. 1994. Hydrophilic and amphiphilic forms of Drosophila choline acetyltransferase are encoded by a single mRNA. Eur J Neurosci 6: 737–745.
Sandmann J, Wurtman RJ. 1990. Phospholipase D and Phospholipase C in human cholinergic neuroblastoma (LA-N-2) cells: Modulation by muscarinic agonists and protein kinase C. In: Biology and Medicine of Signal Transduction, Nishizuka Y, Endo M, Tanaka C, editors. New York: Raven Press; pp. 176–181.
Sandmann J, Wurtman RJ. 1991. Stimulation of phospholipase D activity in human neuroblastoma (LA-N-2) cells by activation of muscarinic acetylcholine receptors or by phorbol esters: Relationship to phosphoinositide turnover. J Neurochem 56: 1312–1319.
Sandmann J, Peralta EG, Wurtman RJ. 1991. Coupling of transfected muscarinic acetylcholine receptor subtypes to phospholipase D. J Biol Chem 266: 6031–6034.
Sandstrom NJ, Loy R, Williams CL. 2002. Prenatal choline supplementation increases NGF levels in the hippocampus and frontal cortex of young and adult rats. Brain Res 947: 9–16.
Savci V, Ulus IH. 1996. Central choline reverses hypotension caused by alpha-adrenoceptor or ganglion blockade in rats: The role of vasopressin. Eur J Pharmacol 311: 153–161.
Savci V, Ulus IH. 1997. Cardiovascular effects of central choline during endotoxin shock in the rat. J Cardiovasc Pharmacol 30: 667–675.
Savci V, Ulus IH. 1998. Choline administration reverses hypotension in spinal cord transected rats: The involvement of vasopressin. Neurochem Res 23: 733–741.
Savci V, Wurtman RJ. 1995. Effect of cytidine on membrane phospholipid synthesis in rat striatal slices. J Neurochem 64: 378–384.
Savci V, Goktalay G, Ulus IH. 2002b. Intracerebroventricular choline increases plasma vasopressin and augments plasma vasopressin response to osmotic stimulation and hemorrhage. Brain Res 942: 58–70.
Savci V, Cavun S, Goktalay G, Ulus IH. 2002a. Cardiovascular effects of intracerebroventricularly injected CDP-choline in normotensive and hypotensive animals: The involvement of cholinergic system. Naunyn Schmiedebergs Arch Pharmacol 365: 388–398.
Savci V, Gurun MS, Cavun S, Ulus IH. 1998. Cardiovascular effects of centrally injected tetrahydroaminoacridine in conscious normotensive rats. Eur J Pharmacol 346: 35–41.
Savci V, Gurun MS, Ulus IH, Kiran BK. 1996. Effect of intracerebroventricularly injected choline on plasma ACTH and beta-endorphin levels in conscious rats. Eur J Pharmacol 309: 275–280.
Savci V, Goktalay G, Cansev M, Cavun S, Yilmaz SM, et al. 2003. Intravenously injected CDP-choline increases blood pressure and reverses hypotension in haemorrhagic shock: Effect is mediated by central cholinergic activation. Eur J Pharmacol 468: 129–139.
Savendahl L, Mar MH, Underwood LE, Zeisel SH. 1997. Prolonged fasting in humans results in diminished plasma choline concentrations but does not cause liver dysfunction. Am J Clin Nutr 66: 622–625.
Sawada N, Takanaga H, Matsuo H, Naito M, Tsuruo T, et al. 1999. Choline uptake by mouse brain capillary endothelial cells in culture. J Pharm Pharmacol 51: 847–852.
Scally MC, Ulus IH, Wurtman RJ. 1978. Choline administration to the rat increases urinary catecholamines. J Neural Transm 43: 103–112.
Schabitz WR, Li F, Irie K, Sandage BW, Locke KW, et al. 1999. Synergistic effects of a combination of low-dose basic fibroblast growth factor and citicoline after temporary experimental focal ischemia. Stroke 30: 427–432.
Schabitz WR, Weber J, Takano K, Sandage BW, Locke KW, et al. 1996. The effects of prolonged treatment with citicoline in temporary experimental focal ischemia. J Neurol Sci 138: 21–25.
Schenk F, Brandner C. 1995. Indirect effects of peri- and postnatal choline treatment on place-learning abilities in rat. Psychobiology 23: 302–313.
Schweifer N, Barlow DP. 1996. The Lx1 gene maps to mouse chromosome 17 and codes for a protein that is homologous to glucose and polyspecific transmembrane transporters. Mamm Genome 7: 735–740.
Seddik R, Bradaia A, Trouslard J. 2003. Choline induces Ca2+ entry in cultured sympathetic neurons isolated from rat superior cervical ganglion. Eur J Pharmacol 471: 165–176.
Selkoe DJ. 2002. Alzheimer's disease is a synaptic failure. Science 298: 789–791.
Shibuya M, Kageyama N, Taniguchi T, Hidaka H, Fujiwara M. 1981. Effects of CDP-choline on striatal dopamine level and behaviour in rats. Jpn J Pharmacol 31: 47–52.
Shuaib A, Yang Y, Li Q. 2000. Evaluating the efficacy of citicoline in embolic ischemic stroke in rats: Neuroprotective effects when used alone or in combination with urokinase. Exp Neurol 161: 733–739.
Simon JR, Kuhar MJ. 1975. Impulse-flow regulation of high affinity choline uptake in brain cholinergic nerve terminals. Nature 255: 162–163.
Singh GS. 1973. Action of choline the rat blood pressure. Indian J Physiol Pharmacol 17: 125
Skold O. 1960. Uridine kinase from Erlich ascites tumor: Purification and properties. J Biol Chem 235: 3273–3279.
Slack BE, Wurtman RJ. 2006. Regulation of synthesis and metabolism of the amyloid precursor protein by extracellular signals. In: Research Progress in Alzheimer's Disease and Dementia, Sun M-K, editor. New York: Nova Publishers (in press).
Slack BE, Breu J, Muchnicki L, Wurtman RJ. 1997. Rapid stimulation of amyloid precursor protein release by epidermal growth factor: Role of protein kinase C. Biochem J 327: 245–249.
Sleight R, Kent C. 1980. Regulation of phosphatidylcholine biosynthesis in cultured chick embryonic muscle treated with phospholipase C. J Biol Chem 255: 10644–10650.
Sleight R, Kent C. 1983. Regulation of phosphatidylcholine biosynthesis in mammalian cells. I. effects of phospholipase C treatment on phosphatidylcholine metabolism in Chinese hamster ovary cells and LM mouse fibroblasts. J Biol Chem 258: 824–830.
Sobrado M, Lopez MG, Carceller F, Garcia AG, Roda JM. 2003. Combined nimodipine and citicoline reduce infarct size, attenuate apoptosis and increase BCL-2 expression after focal ischemia. Neuroscience 118: 107–113.
Soderberg M, Edlund C, Kristensson K, Dallner G. 1991. Fatty acid composition of brain phosholipids in aging and in Alzheimer's disease. Lipids 26: 421–425.
Spanner S, Ansell GB. 1979. Choline kinase and ethanolamine kinase activity in the cytosol of nerve endings from rat forebrain. Biochem J 178: 753–760.
Speth RC, Yamamura HI. 1979. On the ability of choline and its analogues to interact with muscarinic cholinergic receptors in the rat brain. Eur J Pharmacol 58: 197–201.
Spiers PA, Myers D, Hochanadel GS, Lieberman HR, Wurtman RJ. 1996. Citicoline improves verbal memory in aging. Arch Neurol 53: 441–448.
Srimal RC, Jaju BP, Sinha JN, Dixit KS, Bhargava KP. 1969. Analysis of the central vasomotor effects of choline. Eur J Pharmacol 5: 239–244.
Stalenhoef AFH, De Graaf J, Wittekoek ME, Bredie SJH, Demacker PNM, et al. 2000. The effect of concentrated n-3 fatty acids versus gemfibrozil on plasma lipoproteins, low density lipoprotein heterogeneity and oxidizability in patients with hypertriglyceridemia. Atherosclerosis 153: 129–138.
Stavinoha WB, Weintraub ST. 1974. Choline content of rat brain. Science 183: 964–965.
Steigmann F, Firestein R, De La Huerga J. 1952. Intravenous choline therapy. Fed Proc 11: 393
Stoll AL, Cohen BM, Snyder MB, Hanin I. 1991. Erythrocyte choline concentration in bipolar disorder: A predictor of clinical course and medication response. Biol Psychiatry 29: 1171–1180.
Strahlendorf JC, Acosta S, Miles R, Strahlendorf HK. 2001. Choline blocks AMPA-induced dark cell degeneration of Purkinje neurons: Potential role of the a7 nicotinic receptor. Brain Res 901: 71–78.
Streumer-Svobodova Z, Drahota Z. 1977. The development of oxidative enzymes in rat liver mitochondria. Physiol Bohemoslov 26: 525–534.
Sugino Y, Teraoka H, Shimono H. 1966. Metabolism of deoxyribonucleotides. I. Purification and properties of deoxycytidine monophosphokinase of calf thymus. J Biol Chem 241: 961–969.
Sundler R, Arvidson G, Akesson B. 1972. Pathways for the incorporation of choline into rat liver phosphatidylcholines in vivo. Biochim Biophys Acta 280: 559–568.
Suzuki K. 1981. Chemistry and metabolism of brain lipids. In: Basic Neurochemistry, 3rd edn. Siegel GJ, Albers RW, Agranoff BW, Katzman R, editors. Boston: Little, Brown & Co.; pp. 355–370.
Sweet DH, Miller DS, Pritchard JB. 2001. Ventricular choline transport. A role for organic cation transporter 2 expressed in choroid plexus. J Biol Chem 276: 41611–41619.
Tacconi M, Wurtman RJ. 1985. Phosphatidylcholine produced in rat synaptosomes by N-methylation is enriched in polyunsaturated fatty acids. Proc Natl Acad Sci USA 82: 4828–4831.
Takatori T, Tomii S, Terazawa K. 1984. A medicolegal study on enzymic fluorometry of choline in human semen. J Forensic Sci 29: 618–623.
Tamai I, Ohashi R, Nezu J-E, Yabuuchi H, Oku A, et al. 1998. Molecular and functional identification of sodium ion-dependent, high-affinity human carnitine transporter OCTN2. J Biol Chem 273: 20378–20382.
Tang W, Keesler GA, Tabas I. 1997. The structure of the gene for murine CTP: Phosphocholine cytidylyltransferase, Ctpct. Relationship of exon structure to functional domains and identification of transcriptional start sites and potential upstream regulatory elements. J Biol Chem 272: 13146–13151.
Taylor P, Brown JH. 2006. Acetylcholine. In: Basic Neurochemistry, Siegel GJ, Albers RW, Brady ST, Price DL, editors. Boston: Elsevier; pp. 185–209.
Taylor P, Radic Z. 1994. The cholinesterases: From genes to proteins. Annu Rev Pharmacol Toxicol 34: 281–320.
Tazaki Y, Sakai F, Otomo E, Kutsuzawa T, Kameyama M, et al. 1988. Treatment of acute cerebral infarction with a choline precursor in a multicenter double-blind placebo-controlled study. Stroke 19: 211–216.
Teather LA, Wurtman RJ. 2003. Dietary cytidine (5′)-diphosphocholine supplementation protects against development of memory deficits in aging rats. Prog Neuropsychopharmacol Biol Psychiatry 27: 711–717.
Teather LA, Wurtman RJ. 2005. Dietary CDP-choline supplementation prevents memory impairment caused by impoverished environmental conditions in rats. Learn Mem 12: 39–43.
Tees RC. 1999a. The influences of rearing environment and neonatal choline dieatary supplementation on spatial learning and memory in adult rats. Behav Brain Res 105: 173–178.
Tees RC. 1999b. The influences of sex, rearing environment, and neonatal choline dietary supplementation on spatial and non-spatial learning and memory in adult rats. Dev Psychobiol 35: 328–342.
Tees RC, Mohammadi E. 1999. The effects of neonatal choline dietary supplementation on adult spatial and configural learning and memory in rats. Dev Psychobiol 35: 226–240.
Terry RD, Masliah E, Salmon DP, Butters N, De Teresa R, et al. 1991. Physical basis of cognitive alterations in Alzheimer's disease: Synapse loss is the major correlate of cognitive impairment. Ann Neurol 30: 572–580.
Thomas JD, Garrison M, O'Neill TM. 2004. Perinatal choline supplementation attenuates behavioral alterations associated with neonatal alcohol exposure in rats. Neurotoxicol Teratol 26: 35–45.
Tornos ME, Sacristan A, Ortiz JA. 1983a. Pharmacological study of CDP-choline. Protection against toxicity in a model of experimental hypoxia. Arzneimittelforschung 33: 1022–1024.
Tornos ME, Sacristan A, Ortiz JA. 1983b. Effect of oral CDP-choline on experimental withdrawal syndrome. Arzneimittelforschung 33: 1018–1021.
Traut TW. 1994. Physiological concentrations of purines and pyrimidines. Mol Cell Biochem 140: 1–22.
Tronchere H, Record M, Terce F, Chap H. 1994. Phosphatidylcholine cycle and regulation of phosphatidylcholine biosynthesis by enzyme translocation. Biochim Biophys Acta 1212: 137–151.
Trovarelli G, De Medio GE, Montanini I. 1982. The influence of CDP-choline on brain lipid metabolism during ischemia. Farmaco [Sci] 37: 663–668.
Trovarelli G, de Medio GE, Dorman RV, Piccinin GL, Horrocks LA, et al. 1981. Effect of cytidine diphosphophate choline (CDP-choline) on ischemia-induced alterations of brain lipid in the gerbil. Neurochem Res 6: 821–833.
Tsuge H, Nakano Y, Onishi H, Futamura Y, Ohashi K. 1980. A novel purification and some properties of rat liver mitochondrial choline dehydrogenase. Biochim Biophys Acta 614: 274–284.
Tucek S. 1990. The synthesis of acetylcholine: Twenty years of progress. Prog Brain Res 84: 467–477.
Turinsky J, Bayly BP, O'Sullivan DM. 1991. 1,2-diacylglycerol and ceramide levels in rat liver and skeletal muscle in vivo. Am J Physiol 261: E620–E627.
Uchida T. 1994. Immunologically and enzymatically distinct rat choline kinase isozymes. J Biochem (Tokyo) 116: 1241–1250.
Uchida T, Yamashita S. 1990. Purification and properties of choline kinase from rat brain. Biochim Biophys Acta 1043: 281–288.
Uchida T, Yamashita S. 1992. Molecular cloning, characterization, and expression in Escherichia coli of a cDNA encoding mammalian choline kinase. J Biol Chem 267: 10156–10162.
Ulus IH, Wurtman RJ. 1976. Choline administration: Activation of tyrosine hydroxylase in dopaminergic neurons of rat brain. Science 194: 1060–1061.
Ulus IH, Wurtman RJ. 1979. Selective response of rat peripheral sympathetic nervous system to various stimuli. J Physiol 293: 513–523.
Ulus IH, Hirsch MJ, Wurtman RJ. 1977a. Trans-synaptic induction of adrenomedullary tyrosine hydroxylase activity by choline: Evidence that choline administration can increase cholinergic neurotransmission. Proc Natl Acad Sci USA 74: 798–800.
Ulus IH, Ozyurt G, Korfali E. 1998. Decreased serum choline concentrations in humans after surgery, childbirth, and traumatic head injury. Neurochem Res 23: 727–732.
Ulus IH, Scally MC, Wurtman RJ. 1977b. Choline potentiates the induction of adrenal tyrosine hydroxylase by reserpine, probably by enhancing the release of acetylcholine. Life Sci 21: 145–148.
Ulus IH, Scally MC, Wurtman RJ. 1978. Enhancement by choline of the induction of adrenal tyrosine hydroxylase by phenoxybenzamine, 6-hydroxydopamine, insulin or exposure to cold. J Pharmacol Exp Ther 204: 676–682.
Ulus IH, Arslan BY, Savci V, Kiran BK. 1995. Restoration of blood pressure by choline treatment in rats made hypotensive by haemorrhage. Br J Pharmacol 116: 1911–1917.
Ulus IH, Arslan Y, Tanrisever R, Kiran BK. 1979. Postsynaptic effects of choline administration. In: Nutrition and the Brain, Vol. 5. Barbeau A, Growdon JH, and Wurtman RJ, editors. New York: Raven Press; pp. 219–226.
Ulus IH, Millington WR, Buyukuysal RL, Kiran BK. 1988. Choline as an agonist: Determination of its agonistic potency on cholinergic receptors. Biochem Pharmacol 37: 2747–2755.
Ulus IH, Wurtman RJ, Mauron C, Blusztajn JK. 1989. Choline increases acetylcholine release and protects against the stimulation-induced decrease in phosphatide levels within membranes of rat corpus striatum. Brain Res 484: 217–227.
Ulus IH, Watkins CJ, Cansev M, Wurtman RJ. 2006. Cytidine and uridine increase striatal CDP-Choline levels without decreasing acetylcholine synthesis or release. Cell Mol Neurobiol (in press).
Ulus IH, Wurtman RJ, Scally MC, Hirsch MJ. 1977c. Effect of choline on cholinergic function. In: Cholinergic Mechanism and Psychopharmacology, Advances in Behavioral Biology, Vol. 24. Jenden DJ, editor. New York: Plenum Press; pp. 525–537.
Utal AK, Jamil H, Vance DE. 1991. Diacylglycerol signals the translocation of CTP: Choline-phosphate cytidylyltransferase in HeLa cells treated with 12-O-tetradecanoylphorbol-13-acetate. J Biol Chem 266: 24084–24091.
van Rompay AR, Johansson M, Karlsson A. 1999. Phosphorylation of deoxycytidine analog monophosphates by UMP-CMP kinase: Molecular characterization of the human enzyme. Mol Pharmacol 56: 562–569.
van Rompay AR, Norda A, Linden K, Johansson M, Karlsson A. 2001. Phosphorylation of uridine and cytidine analogs by two human uridine-cytidine kinases. Mol Pharmacol 59: 1181–1186.
Vance DE, Pelech SL. 1984. Enzyme translocation in the regulation of phosphatidylcholine biosynthesis. Trends Biochem Sci 9: 17–20.
Vaz FM, Fouchier SW, Ofman R, Sommer M, Wanders RJA. 2000. Molecular and biochemical characterization of rat gamma-trimethylaminobutyraldehyde dehydrogenase and evidence for the involvement of human aldehyde dehydrogenase 9 in carnitine biosynthesis. J Biol Chem 275: 7390–7394.
Velzing-Aarts FV, Holm PI, Fokkema MR, van der Dijs FP, Ueland PM, et al. 2005. Plasma choline and betaine and their relation to plasma homocysteine in normal pregnancy. Am J Clin Nutr 81: 1383–1389.
Vigo C, Vance DE. 1981. Effect of diethylstilboestrol on phosphatidylcholine biosynthesis and choline metabolism in the liver of roosters. Biochem J 200: 321–326.
Wagner AF, Hunt PS. 2006. Impaired trace fear conditioning following neonatal ethanol: Reversal by choline. Behav Neurosci 120: 482–487.
Walkey CJ, Shields DJ, Vance DE. 1999. Identification of three novel cDNAs for human phosphatidylethanolamine N-methyltransferase and localization of the human gene on chromosome 17p11.2. Biochim Biophys Acta 1436: 405–412.
Wang L, Pooler AM, Regan MA, Wurtman RJ. 2004. Uridine increases neurotransmitter release in aged rats. 34th Society for Neuroscience Abstracts, San Diego, CA, USA, 23–27 October.
Wang L, Pooler AM, Regan MA, Wurtman RJ. 2005a. Dietary uridine-5′-monophosphate supplementation increases potassium-induced dopamine release and promotes neurite outgrowth in aged rats. J Mol Neurosci 27: 137–146.
Wang TP, Sable HZ, Lampen JO. 1950. Enzymatic deamination of cytosine nucleosides. J Biol Chem 184: 17–28.
Wang Y, Su D-M, Wang R-H, Liu Y, Wang H. 2005b. Antinociceptive effects of choline against acute and inflammatory pain. Neuroscience 132: 49–56.
Warach S. 2002. Dose dependent reduction in infarct growth with citicoline treatment: Evidence of neuroprotection in human stroke? Stroke 33: 354.
Warach S, Pettigrew LC, Dashe JF, Pullicino P, Lefkowitz DM, et al. 2000. Effect of citicoline on ischemic lesions measured by diffusion-weighed magnetic resonance imaging. Citicoline 010 investigators. Ann Neurol 48: 713–722.
Warden CH, Friedkin M. 1985. Regulation of choline kinase activity and phosphatidylcholine biosynthesis by mitogenic growth factors in 3T3 fibroblasts. J Biol Chem 260: 6006–6011.
Watkins JD, Kent C. 1991. Regulation of CTP:phosphocholine cytidylyltransferase activity and subcellular location by phosphorylation in Chinese hamster ovary cells. The effect of phospholipase C treatment. J Biol Chem 266: 21113–21117.
Wecker L, Rothermal S, Cawley G. 1987. Chronic choline supplementation attenuates the behavioral effects of pentobarbital. Pharmacol Biochem Behav 28: 469–475.
Wecker L, Flynn CJ, Stouse MR, Trommer BA. 1982. Choline availability: Effects on the toxicity of centrally active drugs. Drug Nutr Interact 1: 125–130.
Weinhold PA, Rounsifer ME, Feldman DA. 1986. The purification and characterization of CTP: Phosphorylcholine cytidylyltransferase from rat liver. J Biol Chem 261: 5104–5110.
Weinhold PA, Charles L, Rounsifer ME, Feldman DA. 1991. Control of phosphatidylcholine synthesis in Hep G2 cells. Effect of fatty acids on the activity and immunoreactive content of choline phosphate cytidylyltransferase. J Biol Chem 266: 6093–6100.
Wilgram GF, Kennedy EP. 1963. Intracellular distribution of some enzymes catalyzing reactions in the biosynthesis of complex lipids. J Biol Chem 238: 2615–2619.
Wilken DR, McMacken ML, Rodriquez A. 1970. Choline and betaine aldehyde oxidation by rat liver mitochondria. Biochim Biophys Acta 216: 305–317.
Williams CL, Meck WH, Heyer DD, Loy R. 1998. Hypertrophy of basal forebrain neurons and enhanced visuospatial memory in perinatally choline-supplemented rats. Brain Res 794: 225–238.
Wittenberg J, Kornberg A. 1953. Choline phosphokinase. J Biol Chem 202: 431–444.
Wood PL, Suranyi-Cadotte B, Schwartz G, Nair NPV. 1983. Platelet 3H-imipramine binding and red blood cell choline in affective disorders: Indications of heterogeneous pathogenesis. Biol Psychiatry 18: 715–719.
Wright MM, McMaster CR. 2002. PC and PE synthesis: Mixed micellar analysis of the cholinephosphotransferase and ethanolaminephosphotransferase activities of human choline/ethanolamine phosphotransferase 1 (CEPT1). Lipids 37: 663–672.
Wu X, Gutierrez MM, Giacomini KM. 1994. Further characterization of the sodium-dependent nucleoside transporter (N3) in choroid plexus from rabbit. Biochim Biophys Acta 1191: 190–196.
Wu X, Yuan G, Brett CM, Hui AC, Giacomini KM. 1992. Sodium-dependent nucleoside transport in choroid plexus from rabbit. Evidence for a single transporter for purine and pyrimidine nucleosides. J Biol Chem 267: 8813–8818.
Wurtman RJ, Rose CM. 1970. L-Dihydroxyphenylalanine: Effect on S-Adenosylmethionine in brain. Science 169: 395–397.
Wurtman RJ, Regan M, Ulus I, Yu L. 2000. Effect of oral CDP-choline on plasma choline and uridine levels in humans. Biochem Pharmacol 60: 989–992.
Wurtman RJ, Ulus IH, Cansev M, Watkins CJ, Wang L, et al. 2006. Synaptic proteins and phospholipids are increased in gerbil brain by administering uridine plus docosahexaenoic acid orally. Brain Res 1088: 83–92.
Yamamoto M, Shimizu M, Okamiya M. 1990. Pharmacological actions of a new TRH analogue, YM-14673, in rats subjected to cerebral ischemia and anoxia. Eur J Pharmacol 181: 207–214.
Yamamura HI, Snyder SH. 1972. Choline: High-affinity uptake by rat brain synaptosomes. Science 178: 626–628.
Yamamura HI, Snyder SH. 1973. High affinity transport of choline into synaptosomes of rat brain. J Neurochem 21: 1355–1374.
Yang B, Lin H, Xu C, Liu Y, Wang H, et al. 2005. Choline produces cytoprotective effects against ischemic myocardial injuries: Evidence for the role of cardiac M3 subtype muscarinic acetylcholine receptors. Cell Physiol Biochem 16: 163–174.
Yang Y, Liu Z, Cermak JM, Tandon P, Sarkisian MR, et al. 2000. Protective effects of prenatal choline supplementation on seizure-induced memory impairment. J Neurosci 20: RC109.
Yilmaz MS, Yalcin M, Savci V. 2006b. Cytidine 5′-diphosphocholine restores blood flow of superior mesenteric and renal arteries and prolongs survival time in hemorrhaged anaesthetized rats. Clin Exp Pharmacol Physiol 33: 415–420.
Yilmaz Z, Ilcol YO, Torun S, Ulus IH. 2006a. Intravenous administration of choline or CDP-choline improves platelet count and platelet closure times in endotoxin-treated dogs. Shock 25: 73–79.
Yu V. 2002. Scientific rationale and benefits of nucleotide supplementation of infant formula. J Paediatr Child Health 38: 543–549.
Yucel N, Caylı SR, Ates O, Karadag N, Firat S, et al. 2006. Evaluation of the neuroprotective effects of citicoline after experimental spinal cord injury: Improved behavioral and neuroanatomical recovery. Neurochem Res 31: 767–775.
Zalkin H. 1985. CTP synthase. Methods Enzymol 113: 282–287.
Zeisel SH. 1981. Dietary choline: Biochemistry, physiology and pharmacology. Annu Rev Nutr 1: 95–121.
Zeisel SH. 2000. Choline: An essential nutrient for humans. Nutrition 16: 669–671.
Zeisel SH. 2006. Choline: Critical role during fetal development and dietary requirements in adults. Annu Rev Nutr 26: 229–250.
Zeisel SH, Wurtman RJ. 1981. Developmental changes in rat blood choline concentration. Biochem J 198: 565–570.
Zeisel SH, Epstein MF, Wurtman RJ. 1980a. Elevated choline concentration in neonatal plasma. Life Sci 26: 1827–1831.
Zeisel SH, Mar MH, Zhou Z, da Costa KA. 1995. Pregnancy and lactation are associated with diminished concentrations of choline and its metabolites in rat liver. J Nutr 125: 3049–3054.
Zeisel SH, Story DL, Wurtman RJ, Brunengraber H. 1980b. Uptake of free choline by isolated perfused rat liver. Proc Natl Acad Sci USA 77: 4417–4419.
Zeisel SH, Growdon JH, Wurtman RJ, Magil SG, Logue M. 1980c. Normal plasma choline responses to ingested lecithin. Neurology 30: 1226–1229.
Zeisel SH, da Costa K-A, Franklin PD, Alexander EA, Lamont JT, et al. 1991. Choline, an essential nutrient for humans. FASEB J 5: 2093–2098.
Zhang J, Blusztajn JK, Zeisel SH. 1992. Measurement of the formation of betaine aldehyde and betaine in rat liver mitochondria by a high pressure liquid chromatography-radioenzymatic assay. Biochim Biophys Acta 1117: 333–339.
Zhang L, Dresser MJ, Gray AT, Yost SC, Terashita S, et al. 1997. Cloning and functional expression of a human liver organic cation transporter. Mol Pharmacol 51: 913–921.
Zwart R, Vijverberg HP. 2000. Potentiation and inhibition of neuronal alpha4beta4 nicotinic acetylcholine receptors by choline. Eur J Pharmacol 393: 209–214.
The authors thank Dr. Jan Krzysztof Blustajn and Ms. Carol Watkins for the critical review of this chapter. Studies described in this chapter were supported in part by grants from the National Institutes of Mental Health (MH-28783); the NIH-NCRR (5-MO1RR01066–29); the Center for Brain Sciences and Metabolism Charitable Trust; and the Turkish Academy of Sciences (Ismail H. Ulus).
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Wurtman, R.J., Cansev, M., Ulus, I.H. (2009). Choline and Its Products Acetylcholine and Phosphatidylcholine. In: Lajtha, A., Tettamanti, G., Goracci, G. (eds) Handbook of Neurochemistry and Molecular Neurobiology. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-30378-9_18
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