Abstract
Neurotransmitters and neuropeptides interact in several ways. We studied a new type of interaction: the effect of neurotransmitters on the saturable system that transports Tyr-MIF-1 and the enkephalins out of the central nervous system (CNS). The neurotransmitters were introduced into the lateral ventricle of the brain with radioiodinated peptide, using an established method previously shown to accurately quantify the amount of peptide being transported from the CNS to the blood. Serotonin inhibited transport, histamine stimulated transport, and dopamine, acetylcholine, epinephrine, GABA, kainic acid, cAMP and cGMP were without effect. Cyproheptadine, a serotonin antagonist, stimulated transport. Of several psychotropic agents tested, only tranylcypromine had a statistically significant effect and stimulated transport. Of the serotonin receptor specific agents tested, those with 5HT1 activity most consistently affected transport. We conclude that serotonin, and perhaps histamine, are important modulators of the system that transports Tyr-MIF-1 and the enkephalins out of the CNS.
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Aimone LD, Gebhart GF (1988) Serotonin and/or an excitatory amino acid in the medial medulla mediates stimulation-produced antinociception from the lateral hypothalamus in the rat. Brain Res 450:170–180
Amir S (1984) Naloxone improves, and morphine exacerbates, experimental shock induced by release of endogenous histamine by compound 48/80. Brain Res 297:187–190
Banks WA, Kastin AJ (1983) Aluminum increases permeability of the blood-brain barrier to labeled DSIP and beta-endorphin: possible implications for senile and dialysis dementia. Lancet II:1227–1229
Banks WA, Kastin AJ (1984) A brain-to-blood carrier-mediated transport system for small, N-tyrosinated peptides. Pharmacol Biochem Behav 21:943–946
Banks WA, Kastin AJ (1985a) Permeability of the blood-brain barrier to neuropeptides: the case for penetration. Psychoneuroendocrinology 10:385–399
Banks WA, Kastin AJ (1985b) Aging and the blood-brain barrier: changes in the carrier-mediated transport of peptides in rats. Neurosci Lett 61:171–175
Banks WA, Kastin AJ (1986) Modulation of the carrier-mediated transport of Tyr-MIF-1 across the blood-brain barrier by essential amino acids. J Pharmacol Exp Ther 239:668–672
Banks WA, Kastin AJ (1987) Saturable transport of peptides across the blood-brain barrier. Life Sci 41:1319–1338
Banks WA, Kastin AJ (1988a) Twenty-one hormones fail to inhibit the brain to blood transport system for Tyr-MIF-1 and the enkephalins in mice. J Pharm Pharmacol 40:289–291
Banks WA, Kastin AJ (1988b) Peptides and the senescent blood-brain barrier. Neurobiol Aging 9:48–49
Banks WA, Kastin AJ (1988c) Interactions between the blood-brain barrier and endogenous peptides: emerging clinical implications. Am J Med Sci 295:459–465
Banks WA, Kastin AJ (1989) Inhibition of the brain to blood transport system for enkephalins and Tyr-MIF-1 in mice addicted or genetically predisposed to drinking ethanol. Alcohol 6:53–57
Banks WA, Kastin AJ, Coy DH (1984) Evidence that 125I-N-Tyr-delta sleep-inducing peptide crosses the blood-brain barrier by a non-competitive mechanism. Brain Res 301:201–207
Banks WA, Kastin AJ, Michals EA (1985) Transport of thyroxine across the blood-brain barrier is directed primarily from the brain to the blood. Life Sci 37:2407–2414
Banks WA, Kastin AJ, Fischman AJ, Coy DH, Strauss SL (1986) Carrier-mediated transport of enkephalins and N-Tyr-MIF-1 across the blood-brain barrier. Am J Physiol 251:E477-E482
Banks WA, Kastin AJ, Michals EA (1987a) Tyr-MIF-1 and methionine enkephalin share a saturable blood-brain barrier transport system. Peptides 8:890–903
Banks WA, Kastin AJ, Horvath A, Michals EA (1987b) Carrier-mediated transport of vasopressin across the blood-brain barrier of the mouse. J Neurosci Res 18:326–332
Banks WA, Kastin AJ, Fasold MB (1988a) Differential effect of aluminum on the blood-brain barrier transport of peptides, technetium and albumin. J Pharmacol Exp Ther 244:579–585
Banks WA, Kastin AJ, Fasold MB, Barrera CM, Augereau G (1988b) Studies of the slow bidirectional transport of iron and transferrin across the blood-brain barrier. Brain Res Bull 21:881–885
Banks WA, Kastin AJ, Nager BJ (1988c) Analgesia and the blood-brain barrier transport system for Tyr-MIF-1/enkephalins: evidence for a dissociation. Neuropharmacology 27:175–179
Banks WA, Kastin AJ, Trentman TL, Haynes HS, Johnson BG, Galina ZH (1988d) Mediation of serotonin-induced analgesia by the 5HT2 receptor in the pentobarbital anesthetized mouse model. Brain Res Bull 21:887–891
Barrera CM, Kastin AJ, Banks WA (1987) d-[Ala1]-peptide T-amide is transported from the blood to the brain by a saturable system. Brain Res Bull 19:629–633
Begley DJ, Chain DG, (1981) Clearance of [3H-Tyr]leucine encephalin from rabbit cerebrospinal fluid. J Physiol (Lond) 319:40–41P
Brase DA (1979) Roles of serotonin and gamma-amino butyric acid in opioid effects. In: Loh HH, Ross DH (eds) Advanced biochemistry and psychopharmacology 20. Raven Press, New York, pp 409–428
Blum K, Briggs AH, Elston SFA, DeLallo L, Sheridan PJ (1982) Reduced leucine-enkephalin-like immunoreactive substance in hamster basal ganglia after long-term ethanol exposure. Science 216:1425–1427
Blum K, Elston SFA, DeLallo L, Briggs AH, Wallace JE (1983) Ethanol acceptance as a function of genotype amounts of brain [Met]enkephalin. Proc Natl Acad Sci USA 80:6510–6512
Copland AM, Balfour DJK (1987) The effects of diazepam on brain 5-HT and 5-HIAA in stressed and unstressed rats. Pharmacol Biochem Behav 27:619–624
Dellavedova L, Parenti M, Tirone F, Groppetti A (1982) Interactions between serotonergic and enkephalinergic neurons in rat striatum and hypothalamus. Eur J Pharmacol 85:29–34
Duka T, Wuster M, Herz A (1979) Rapid changes in enkephalin levels in rat striatum and hypothalamus induced by diazepam. Naunyn-Schmiedeberg's Arch Pharmacol 309:1–5
Duka T, Wuster M, Harz A (1980) Benzodiazepines modulate striatal enkephalin levels via a gabaergic mechanism. Life Sci 26:771–776
Firemark HM (1983) Choroid-plexus transport of enkephalins and other neuropeptides. In: Wood JH (ed) Neurobiology of cercbrospinal fluid 2. Plenum press, New York, pp 77–81
Galina ZH, Kastin AJ (1986) Existence of antiopiate systems as illustrated by MIF-1/Tyr-MIF-1. Life Sci 39:2153–2159
Gill K, Amit Z (1987) Effects of serotonin uptake blockade on food, water, and ethanol consumption in rats. Alcoholism: Clin Exp Res 11:444–449
Giral P, Martin P, Soubrie P, Simon P (1988) Reversal of helpless behavior in rats by putative-5-HT1A agonists. Biol Psychiatry 23:237–242
Goldstein DJ, Kulakowski EC, Ropchak TG, Brown P, Keiser HR (1987) Naloxone reverses the serotonin dependent hypotensive action of CGP 6085A. Life Sci 41:1369–1373
Gothert M, Schlicker E (1987) Classification of serotonin receptors. J Cardiovasc Pharmacol [Suppl 3] 10:S3-S7
Henry JL (1982) Circulating opioids: possible physiological roles in central nervous function. Neurosci Biobehav Rev 6:229–245
Hill SY (1974) Intraventricular injection of 5-hydroxytryptamine and alcohol consumption in rats. Biol Psychiatry 8:151–158
Hong JS, Grimes L, Kanamatsu T, McGinty JF (1987) Kainic acid as a tool to study the regulation and function of opioid peptides in the hippocampus. Toxicology 46:141–157
Hoyer D (1988a) Functional correlates of serotonin 5-HT1 recognition sites. J recept Res 8:59–81
Hoyer D (1988b) Molecular pharmacology and biology of 5-HT1C receptors. TIPS 9:89–94
Huang JT (1984) Accumulation of amino acid and peptide by choroid plexus of the aging rat. Age 7:63–65
Huang JT, Lajtha A (1978) The accumulation of (3H)enkephalinamide (2-d-alanine-5-methioninamide) in rat brain tissues. Neuropharmacology 17:1075–1079
Inase M, Nakahama H, Otsuki T, Fang J (1987) Analgesic effects of serotonin microinjection into nucleus raphe magnus and nucleus raphe dorsalis evaluated by the monosodium urate (MSU) tonic pain model in the rat. Brain Res 426:205–211
Kastin AJ, Nissen C, Coy DH (1981) Permeability of the blood-brain barrier to DSIP peptides. Pharmacol Biochem Behav 15:955–959
Kastin AJ, Banks WA, Zadina JE, Graf M (1983) Brain peptides: dangers of constricted nomenclatures. Life Sci 32:295–301
Kastin AJ, Abel DA, Ehrensing RH, Coy DH, Graf MV (1984) Tyr-MIF-1 and MIF-1 are active in the water wheel test for antidepressant drugs. Pharmacol Biochem Behav 21:767–771
Kelly SJ, Franklin KBJ (1984a) Evidence that stress augments morphine analgesia by increasing brain tryptophan. Neurosci Lett 44:305–310
Kelly SJ, Franklin KBJ (1984b) Electrolytic raphe magnus lesions block analgesia induced by a stress-morphine interaction but not analgesia induced by morphine alone. Neurosci Lett 52:147–152
Kelly SJ, Franklin KBJ (1985) An increase in tryptophan in brain may be a general mechanism for the effect of stress on sensitivity to pain. Neuropharmacology 24:1019–1025
Kennett GA, Dourish CT, Curzon G (1987) Antidepressant-like action of 5-HT1A agonists and conventional antidepressants in an animal model of depression. Eur J Pharmacol 134:265–274
Li T-K, Lumeng L, McBride WJ, Murphy JM (1987) Rodent lines selected for factors affecting alcohol consumption. Alcohol Alcohol [Suppl] 1:91–96
Linnoila M, Eckardt M, Durcan M, Lister R, Martin P (1987) Interactions of serotonin with ethanol: clinical and animal studies. Psychopharmacol Bull 23:452–457
Miller LG, Kastin AJ (1987) MIF-1 and Tyr-MIF-1 augment GABA-stimulated benzodiazepine receptor binding. Peptides 8:751–755
Miller LH, Turnbull BA, Kastin AJ, Coy DH (1986) Sleep-wave activity of a delta sleep-inducing peptide analog correlates with its penetrance of the blood-brain barrier. Sleep 9:80–84
Murphy JM, McBride WJ, Lumeng L, Li T-K (1986) Alcohol preference and regional brain monoamine contents of N/NIH heterogeneous stock rats. Alcohol Drug Res 7:33–39
Murphy JM, McBride WJ, Lumeng L, Li T-K (1987) Contents of monoamines in forebrain regions of alcohol-preferring (P) and -nonpreferring (NP) lines of rats. Pharmacol Biochem Behav 26:389–392
Navarro HA, Aloyo VJ, Rush ME, Walker RF (1987) Serotonin pharmacodynamics in hypothalamic tissues from young and old female rats. Brain Res 421:291–296
Pazos A, Palacios JM (1985) Quantitative autoradiographic mapping of serotonin receptors in the rat brain. I. Serotonin-1 receptors. Brain Res 346:205–230
Pelletier G, Labrie F, Kastin AJ, Coy D, Schally AV (1975) Radioautographic localization of radioactivity in rat brain after intraventricular or intracarotid injection of 3H-L-prolyl-l-leucyl glycinamide. Pharmacol Biochem Behav 3:675–679
Porro CA, Carli G (1988) Immobilization and restraint effects on pain reactions in animals. Pain 32:289–307
Pulvirenti L, Kastin AJ (1988) Blockade of brain dopamine receptors antagonizes the anti-immobility effect of MIF-1 and Tyr-MIF-1 in rats. Eur J Pharmacol 151:289–292
Riekkinen P, Legros J-J, Sennef C, Jolkkonen J, Smitz S, Soininen H (1987) Penetration of DGAVP (Org 5667) across the blood-brain barrier in human subjects. Peptides 8:261–265
Roberts MHT (1984) 5-Hydroxytryptamine and antinociception. Neuropharmacology 23:1529–1536
Rockman GE, Amit Z, Carr G, Brown Z, Ogren SO (1979a) Attenuation of ethanol intake by 5-hydroxytryptamine uptake blockade in laboratory rats. I. Involvement of brain 5-hydroxytryptamine in the mediation of the positive reinforcing properties of ethanol. Arch Int Pharmacodyn Ther 241:245–259
Rockman GE, Amit Z, Carr G, Ogren SO (1979b) Attenuation of ethanol intake by 5-hydroxytryptamine uptake blockade in laboratory rats. II. Possible interaction with brain norepinephrine. Arch Int Pharmacodyn Ther 241:260–265
Sewell RDE, Spencer PSJ (1974) Modification of the antinociceptive activity of narcotic agonists and antagonists by intraventricular injection of biogenic amines in mice. Proc BPS March: 140P–141P
Traber J, Glaser T (1987) 5-HT1A receptor-related anxiolytics. TIPS 8:432–437
Vakulina OP, Tigranyan RA, Brusov OS (1985) Opioid peptide levels in the brain and blood of rats with immobilization stress. Bull Exp Biol Med 98:1484–1486
Wallum BJ, Taborsky Jr GJ, Porte Jr D, Figlewicz DP, Jacobson L, Beard JC, Ward WK, Dorsa D (1987) Cerebrospinal fluid insulin levels increase during intravenous insulin infusions in man. J Clin Endocrinol Metab 64:190–194
Won SJ, Lin MT (1988) 5-Hydroxytryptamine receptors in the hypothalamus mediate thermoregulatory responses in rabbits. Naunyn-Schmiedeberg's Arch Pharmacol 338:256–261
Wong DT, Lumeng L, Threlkeld PG, Reid LR, Li T-K (1988) Serotonergic and adrenergic receptors in alcohol-preferring and non-preferring rats. J Neurol Transm 71:207–218
Woods SC, Porte Jr D (1977) Relationship between plasma and cerebrospinal fluid insulin levels of dogs. Am J Physiol 233:E331-E334
Wozniak KM, Aulakh CS, Hill JL, Murphy DL (1988) The effect of 8-OH-DPAT on temperature in the rat and its modification by chronic antidepressant treatments. Pharmacol Biochem Behav 30:451–456
Yagaloff KA, Hartig PR (1985) Solubilization and characterization of the serotonin 5-HT1C site from pig choroid plexus. Mol Pharmacol 29:120–125
Yagaloff KA, Lozano G, Van Dyke T, Levine AJ, Hartig PR (1986) Serotonin 5-HT1C receptors are expressed at high density on choroid plexus tumors from transgenic mice. Brain Res 385:389–394
Zadina JE, Banks WA, Kastin AJ (1986) Central nervous system effects of peptides 1980–1985: a cross listing of peptides and their central actions from the first six years of the journal Peptides. Peptides 7:497–537
Zlokovic BV, Segal MB, Davson H, Jankov RM (1988) Passage of delta sleep-inducing peptide (DSIP) across the blood-cerebrospinal fluid barrier. Peptides 9:533–538
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Banks, W.A., Kastin, A.J. Effect of neurotransmitters on the system that transports Tyr-MIF-1 and the enkephalins across the blood-brain barrier: a dominant role for serotonin. Psychopharmacology 98, 380–385 (1989). https://doi.org/10.1007/BF00451691
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DOI: https://doi.org/10.1007/BF00451691