Skip to main content
SpringerLink
Log in
Book cover

Adenosine pp 71–85Cite as

Adenosine and Autocrine Metabolic Regulation of Neuronal Activity

  • Chapter
  • First Online:

Abstract

The cause-and-effect relationships between altered metabolism and neurological conditions are not fully understood. However, some metabolic conditions including ischemia/hypoxia, fasting and ketogenic diet therapy are known to modulate processes in the nervous system such as neuroprotection and seizures, indicating that altered metabolism can regulate neuronal excitability. Adenosine is one of the agents linking metabolism to neuronal activity. In this chapter, we discuss purinergic signaling via ATP release and subsequent activation of adenosine receptors, revealing a CNS pathway for metabolic autocrine regulation. ATP is the final product of brain energy metabolism and it can be an indicator of brain metabolic changes. ATP can be released to the extracellular space through sites including gap junction hemichannels, vesicles, and chloride channels. After subsequent dephosphorylation of ATP by ectonucleotidases, the resulting metabolite adenosine can activate adenosine receptors to limit neuronal excitability. All the proteins for purinergic signaling (ATP releasing sites, ectonucleotidases, and adenosine receptors) may be expressed in the same cell, allowing for autocrine regulation. We give one example: our finding of adenosinergic autoregulation through a cascade involving pannexin-1 channels, adenosine A1 receptors, and ATP-sensitive potassium channels in hippocampal CA3 pyramidal neurons. These neurons can react to changes in ATP and glucose levels with altered electrical activity through this purinergic signaling pathway. This pathway may underlie effects seen in ischemic conditions or during ketogenic diet treatment. Adenosinergic autocrine regulation might have a significant role in neuroprotection and seizure regulation in the CNS.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  • Anderson CM, Bergher JP, Swanson RA (2004) ATP-induced ATP release from astrocytes. J Neurochem 88:246–256

    CAS  PubMed  Google Scholar 

  • Andoh T, Ishiwa D, Kamiya Y, Echigo N, Goto T, Yamada Y (2006) A1 adenosine receptor-mediated modulation of neuronal ATP-sensitive K channels in rat substantia nigra. Brain Res 1124:55–61

    CAS  PubMed  Google Scholar 

  • Anschel DJ, Ortega EL, Kraus AC, Fisher RS (2004) Focally injected adenosine prevents seizures in the rat. Exp Neurol 190:544–547

    CAS  PubMed  Google Scholar 

  • Baldwin SA, Beal PR, Yao SY, King AE, Cass CE, Young JD (2004) The equilibrative nucleoside transporter family, SLC29. Pflugers Arch 447:735–743

    CAS  PubMed  Google Scholar 

  • Ballanyi K (2004) Protective role of neuronal KATP channels in brain hypoxia. J Exp Biol 207:3201–3212

    CAS  PubMed  Google Scholar 

  • Ballarin M, Fredholm BB, Ambrosio S, Mahy N (1991) Extracellular levels of adenosine and its metabolites in the striatum of awake rats: inhibition of uptake and metabolism. Acta Physiol Scand 142:97–103

    CAS  PubMed  Google Scholar 

  • Biber K, Klotz KN, Berger M, Gebicke-Härter PJ, van Calker D (1997) Adenosine A1 receptor-mediated activation of phospholipase C in cultured astrocytes depends on the level of receptor expression. J Neurosci 17:4956–4964

    CAS  PubMed  Google Scholar 

  • Bough KJ, Wetherington J, Hassel B, Pare JF, Gawryluk JW, Greene JG, Shaw R, Smith Y, Geiger JD, Dingledine RJ (2006) Mitochondrial biogenesis in the anticonvulsant mechanism of the ketogenic diet. Ann Neurol 60:223–235

    CAS  PubMed  Google Scholar 

  • Brundege JM, Diao L, Proctor WR, Dunwiddie TV (1997) The role of cyclic AMP as a precursor of extracellular adenosine in the rat hippocampus. Neuropharmacology 36:1201–1210

    CAS  PubMed  Google Scholar 

  • Chen Y, Rathbone MP, Hertz L (2001) Guanosine-induced increase in free cytosolic calcium concentration in mouse astrocytes in primary cultures: does it act on an A3 adenosine receptor? J Neurosci Res 65:184–189

    CAS  PubMed  Google Scholar 

  • Coco S, Calegari F, Pravettoni E, Pozzi D, Taverna E, Rosa P, Matteoli M, Verderio C (2003) Storage and release of ATP from astrocytes in culture. J Biol Chem 278:1354–1362

    CAS  PubMed  Google Scholar 

  • Cunha RA, Ribeiro JA, Sebastião AM (1994) Purinergic modulation of the evoked release of [3  H]acetylcholine from the hippocampus and cerebral cortex of the rat: role of the ectonucleotidases. Eur J Neurosci 6:33–42

    CAS  PubMed  Google Scholar 

  • Darby M, Kuzmiski JB, Panenka W, Feighan D, MacVicar BA (2003) ATP released from astrocytes during swelling activates chloride channels. J Neurophysiol 89:1870–1877

    CAS  PubMed  Google Scholar 

  • Davalos D, Grutzendler J, Yang G, Kim JV, Zuo Y, Jung S, Littman DR, Dustin ML, Gan WB (2005) ATP mediates rapid microglial response to local brain injury in vivo. Nat Neurosci 8:752–758

    CAS  PubMed  Google Scholar 

  • Davis LM, Pauly JR, Readnower RD, Rho JM, Sullivan PG (2008) Fasting is neuroprotective following traumatic brain injury. J Neurosci Res 86:1812–1822

    CAS  PubMed  Google Scholar 

  • Deng-Bryant Y, Prins ML, Hovda DA, Harris NG (2011) Ketogenic diet prevents alterations in brain metabolism in young but not adult rats after traumatic brain injury. J Neurotrauma 28:1813–1825

    PubMed  Google Scholar 

  • DeVivo DC, Leckie MP, Ferrendelli JS, McDougal DB Jr (1978) Chronic ketosis and cerebral metabolism. Ann Neurol 3:331–337

    CAS  PubMed  Google Scholar 

  • Dixon AK, Gubitz AK, Sirinathsinghji DJ, Richardson PJ, Freeman TC (1996) Tissue distribution of adenosine receptor mRNAs in the rat. Br J Pharmacol 118:1461–1468

    CAS  PubMed  Google Scholar 

  • Dunwiddie TV (1999) Adenosine and suppression of seizures. Adv Neurol 79:1001–1010

    CAS  PubMed  Google Scholar 

  • Dunwiddie TV, Diao L (2000) Regulation of extracellular adenosine in rat hippocampal slices is temperature dependent: role of adenosine transporters. Neuroscience 95:81–88

    CAS  PubMed  Google Scholar 

  • Dunwiddie TV, Diao L, Proctor WR (1997) Adenine nucleotides undergo rapid, quantitative conversion to adenosine in the extracellular space in rat hippocampus. J Neurosci 17:7673–7682

    CAS  PubMed  Google Scholar 

  • Dunwiddie TV, Hoffer BJ (1980) Adenine nucleotides and synaptic transmission in the in vitro rat hippocampus. Br J Pharmacol 69:59–68

    CAS  PubMed  Google Scholar 

  • Dunwiddie TV, Masino SA (2001) The role and regulation of adenosine in the central nervous system. Annu Rev Neurosci 24:31–55

    CAS  PubMed  Google Scholar 

  • El-Mallakh RS, Paskitti ME (2001) The ketogenic diet may have mood-stabilizing properties. Med Hypotheses 57:724–726

    CAS  PubMed  Google Scholar 

  • Ferré S, Ciruela F, Woods AS, Lluis C, Franco R (2007) Functional relevance of neurotransmitter receptor heteromers in the central nervous system. Trends Neurosci 30:440–446

    PubMed  Google Scholar 

  • Fields RD, Ni Y (2010) Nonsynaptic communication through ATP release from volume-activated anion channels in axons. Sci Signal 3:73

    Google Scholar 

  • Fowler JC (1993) Purine release and inhibition of synaptic transmission during hypoxia and hypoglycemia in rat hippocampal slices. Neurosci Lett 157:83–86

    CAS  PubMed  Google Scholar 

  • Fredholm BB (1995) Purinoceptors in the nervous system. Pharmacol Toxicol 76:228–239

    CAS  PubMed  Google Scholar 

  • Fredholm BB (1997) Adenosine and neuroprotection. Int Rev Neurobiol 40:259–280

    CAS  PubMed  Google Scholar 

  • Fredholm BB, Arslan G, Halldner L, Kull B, Schulte G, Wasserman W (2000) Structure and function of adenosine receptors and their genes. Naunyn Schmiedebergs Arch Pharmacol 362:364–374

    CAS  PubMed  Google Scholar 

  • Fredholm BB, Lindström K, Wallman-Johansson A (1994) Propentofylline and other adenosine transport inhibitors increase the efflux of adenosine following electrical or metabolic stimulation of rat hippocampal slices. J Neurochem 62:563–573

    CAS  PubMed  Google Scholar 

  • Freeman JM, Kossoff EH, Hartman AL (2007) The ketogenic diet: one decade later. Pediatrics 119:535–543

    PubMed  Google Scholar 

  • Frenguelli BG, Llaudet E, Dale N (2003) High-resolution real-time recording with microelectrode biosensors reveals novel aspects of adenosine release during hypoxia in rat hippocampal slices. J Neurochem 86:1506–1515

    CAS  PubMed  Google Scholar 

  • Frenguelli BG, Wigmore G, Llaudet E, Dale N (2007) Temporal and mechanistic dissociation of ATP and adenosine release during ischaemia in the mammalian hippocampus. J Neurochem 101:1400–1413

    CAS  PubMed  Google Scholar 

  • Garré JM, Retamal MA, Cassina P, Barbeito L, Bukauskas FF, Sáez JC, Bennett MV, Abudara V (2010) FGF-1 induces ATP release from spinal astrocytes in culture and opens pannexin and connexin hemichannels. Proc Natl Acad Sci U S A 107:22659–22664

    PubMed  Google Scholar 

  • Goodman RR, Snyder SH (1982) Autoradiographic localization of adenosine receptors in rat brain using [3H] cyclohexyladenosine. J Neurosci 2:1230–1241

    CAS  PubMed  Google Scholar 

  • Gray JH, Owen RP, Giacomini KM (2004) The concentrative nucleoside transporter family, SLC28. Pflugers Arch 447:728–734

    CAS  PubMed  Google Scholar 

  • Greene AE, Todorova MT, McGowan R, Seyfried TN (2001) Caloric restriction inhibits seizure susceptibility in epileptic EL mice by reducing blood glucose. Epilepsia 42:1371–1378

    CAS  PubMed  Google Scholar 

  • Greene AE, Todorova MT, Seyfried TN (2003) Perspectives on the metabolic management of epilepsy through dietary reduction of glucose and elevation of ketone bodies. J Neurochem 86:529–537

    CAS  PubMed  Google Scholar 

  • Hallböök T, Köhler S, Rosén I, Lundgren J (2007) Effects of ketogenic diet on epileptiform activity in children with therapy resistant epilepsy. Epilepsy Res 77:134–140

    PubMed  Google Scholar 

  • Hansen AJ, Hounsgaard J, Jahnsen H (1982) Anoxia increases potassium conductance in hippocampal nerve cells. Acta Physiol Scand 115:301–310

    CAS  PubMed  Google Scholar 

  • Hartman AL, Lyle M, Rogawski MA, Gasior M (2008) Efficacy of the ketogenic diet in the 6-Hz seizure test. Epilepsia 49:334–339

    PubMed  Google Scholar 

  • Henderson GB, Strauss BP (1991) Evidence for cAMP and cholate extrusion in C6 rat glioma cells by a common anion efflux pump. J Biol Chem 266:1641–1645

    CAS  PubMed  Google Scholar 

  • Hertz L, Peng L, Dienel GA (2007) Energy metabolism in astrocytes: high rate of oxidative metabolism and spatiotemporal dependence on glycolysis/glycogenolysis. J Cereb Blood Flow Metab 27:219–249

    CAS  PubMed  Google Scholar 

  • Hu K, Li GR, Nattel S (1999) Adenosine-induced activation of ATP-sensitive K+ channels in excised membrane patches is mediated by PKC. Am J Physiol 276:H488–495

    CAS  PubMed  Google Scholar 

  • Huttenlocher PR (1976) Ketonemia and seizures: metabolic and anticonvulsant effects of two ketogenic diets in childhood epilepsy. Pediatr Res 10:536–540

    CAS  PubMed  Google Scholar 

  • Inoue K (1998) ATP receptors for the protection of hippocampal functions. Jpn J Pharmacol 78:405–410

    CAS  PubMed  Google Scholar 

  • Iwabuchi S, Kawahara K (2011) Functional significance of the negative-feedback regulation of ATP release via pannexin-1 hemichannels under ischemic stress in astrocytes. Neurochem Int 58:376–384

    CAS  PubMed  Google Scholar 

  • Johansson B, Halldner L, Dunwiddie TV, Masino SA, Poelchen W, Gimenez-Llort L, Escorihuela RM, Fernandez-Teruel A, Wiesenfeld-Hallin Z, Xu XJ et al (2001) Hyperalgesia, anxiety, and decreased hypoxic neuroprotection in mice lacking the adenosine A1 receptor. Proc Natl Acad Sci U S A 98:9407–9412

    CAS  PubMed  Google Scholar 

  • Jonzon B, Fredholm BB (1985) Release of purines, noradrenaline, and GABA from rat hippocampal slices by field stimulation. J Neurochem 44:217–224

    CAS  PubMed  Google Scholar 

  • Joseph SM, Buchakjian MR, Dubyak GR (2003) Colocalization of ATP release sites and ecto-ATPase activity at the extracellular surface of human astrocytes. J Biol Chem 278:23331–23342

    CAS  PubMed  Google Scholar 

  • Kaminogo M, Suyama K, Ichikura A, Onizuka M, Shibata S (1998) Anoxic depolarization determines ischemic brain injury. Neurol Res 20:343–348

    CAS  PubMed  Google Scholar 

  • Kang J, Kang N, Lovatt D, Torres A, Zhao Z, Lin J, Nedergaard M (2008) Connexin 43 hemichannels are permeable to ATP. J Neurosci 28:4702–4711

    CAS  PubMed  Google Scholar 

  • Kann O, Kovács R (2007) Mitochondria and neuronal activity. Am J Physiol Cell Physiol 292:C641–C657

    CAS  PubMed  Google Scholar 

  • Kawamura M Jr, Kawamura M (2011) Long-term facilitation of spontaneous calcium oscillations in astrocytes with endogenous adenosine in hippocampal slice cultures. Cell Calcium 49:249–258

    CAS  PubMed  Google Scholar 

  • Kawamura M Jr, Ruskin DN, Masino SA (2010) Metabolic autocrine regulation of neurons involves cooperation among pannexin hemichannels, adenosine receptors, and KATP channels. J Neurosci 30:3886–3895

    CAS  PubMed  Google Scholar 

  • Kraft BD, Westman EC (2009) Schizophrenia, gluten, and low-carbohydrate, ketogenic diets: a case report and review of the literature. Nutr Metab (Lond) 6:10

    Google Scholar 

  • Kulik A, Trapp S, Ballanyi K (2000) Ischemia but not anoxia evokes vesicular and Ca2+-independent glutamate release in the dorsal vagal complex in vitro. J Neurophysiol 83:2905–2915

    CAS  PubMed  Google Scholar 

  • Latini S, Pedata F (2001) Adenosine in the central nervous system: release mechanisms and extracellular concentrations. J Neurochem 79:463–484

    CAS  PubMed  Google Scholar 

  • Liu GJ, Kalous A, Werry EL, Bennett MR (2006) Purine release from spinal cord microglia after elevation of calcium by glutamate. Mol Pharmacol 70:851–859

    CAS  PubMed  Google Scholar 

  • Liu HT, Sabirov RZ, Okada Y (2008a) Oxygen-glucose deprivation induces ATP release via maxi-anion channels in astrocytes. Purinergic Signal 4:147–154

    CAS  PubMed  Google Scholar 

  • Liu HT, Toychiev AH, Takahashi N, Sabirov RZ, Okada Y (2008b) Maxi-anion channel as a candidate pathway for osmosensitive ATP release from mouse astrocytes in primary culture. Cell Res 18:558–565

    CAS  PubMed  Google Scholar 

  • Lloyd HG, Lindström K, Fredholm BB (1993) Intracellular formation and release of adenosine from rat hippocampal slices evoked by electrical stimulation or energy depletion. Neurochem Int 23:173–185

    CAS  PubMed  Google Scholar 

  • MacVicar BA, Thompson RJ (2009) Non-junction functions of pannexin-1 channels. Trends Neurosci 33:93–102

    PubMed  Google Scholar 

  • Madry C, Haglerod C, Attwell D (2010) The role of pannexin hemichannels in the anoxic depolarization of hippocampal pyramidal cells. Brain 133:3755–3763

    PubMed  Google Scholar 

  • Mahan LC, McVittie LD, Smyk-Randall EM, Nakata H, Monsma FJ Jr, Gerfen CR, Sibley DR (1991) Cloning and expression of an A1 adenosine receptor from rat brain. Mol Pharmacol 40:1–7

    CAS  PubMed  Google Scholar 

  • Mantis JG, Centeno NA, Todorova MT, McGowan R, Seyfried TN (2004) Management of multifactorial idiopathic epilepsy in EL mice with caloric restriction and the ketogenic diet: role of glucose and ketone bodies. Nutr Metab (Lond) 1:11

    Google Scholar 

  • Martín ED, Fernández M, Perea G, Pascual O, Haydon PG, Araque A, Ceña V (2007) Adenosine released by astrocytes contributes to hypoxia-induced modulation of synaptic transmission. Glia 55:36–45

    PubMed  Google Scholar 

  • Masino SA, Diao L, Illes P, Zahniser NR, Larson GA, Johansson B, Fredholm BB, Dunwiddie TV (2002) Modulation of hippocampal glutamatergic transmission by ATP is dependent on adenosine A1 receptors. J Pharmacol Exp Ther 303:356–363

    CAS  PubMed  Google Scholar 

  • Masino SA, Geiger JD (2008) Are purines mediators of the anticonvulsant/neuroprotective effects of ketogenic diets? Trends Neurosci 31:273–278

    CAS  PubMed  Google Scholar 

  • Masino SA, Kawamura M, Wasser CA, Pomeroy LT, Ruskin DN (2009) Adenosine, ketogenic diet and epilepsy: the emerging therapeutic relationship between metabolism and brain activity. Curr Neuropharmacol 7:257–268

    CAS  PubMed  Google Scholar 

  • Masino SA, Latini S, Bordini F, Pedata F, Dunwiddie TV (2001) Changes in hippocampal adenosine efflux, ATP levels, and synaptic transmission induced by increased temperature. Synapse 41:58–64

    CAS  PubMed  Google Scholar 

  • Masino SA, Li T, Theofilas P, Sandau US, Ruskin DN, Fredholm BB, Geiger JD, Aronica E, Boison D (2011) A ketogenic diet suppresses seizures in mice through adenosine A1 receptors. J Clin Invest 121:2679–2683

    CAS  PubMed  Google Scholar 

  • Miller LP, Hsu C (1992) Therapeutic potential for adenosine receptor activation in ischemic brain injury. J Neurotrauma 9(Suppl 2):S563–577

    PubMed  Google Scholar 

  • Muzykewicz DA, Lyczkowski DA, Memon N, Conant KD, Pfeifer HH, Thiele EA (2009) Efficacy, safety, and tolerability of the low glycemic index treatment in pediatric epilepsy. Epilepsia 50:1118–1126

    CAS  PubMed  Google Scholar 

  • Nakazawa M, Kodama S, Matsuo T (1983) Effects of ketogenic diet on electroconvulsive threshold and brain contents of adenosine nucleotides. Brain Dev 5:375–380

    CAS  PubMed  Google Scholar 

  • Nylen K, Velazquez JL, Sayed V, Gibson KM, Burnham WM, Snead OC 3rd (2009) The effects of a ketogenic diet on ATP concentrations and the number of hippocampal mitochondria in Aldh5a1 -/- mice. Biochim Biophys Acta 1790:208–212

    CAS  PubMed  Google Scholar 

  • Oláh J, Klivényi P, Gardián G, Vécsei L, Orosz F, Kovacs GG, Westerhoff HV, Ovádi J (2008) Increased glucose metabolism and ATP level in brain tissue of Huntington’s disease transgenic mice. FEBS J 275:4740–4755

    PubMed  Google Scholar 

  • Pan JW, Bebin EM, Chu WJ, Hetherington HP (1999) Ketosis and epilepsy: 31P spectroscopic imaging at 4.1T. Epilepsia 40:703–707

    CAS  PubMed  Google Scholar 

  • Pan WJ, Osmanović SS, Shefner SA (1995) Characterization of the adenosine A1 receptor-activated potassium current in rat locus ceruleus neurons. J Pharmacol Exp Ther 273:537–544

    CAS  PubMed  Google Scholar 

  • Pankratov Y, Lalo U, Verkhratsky A, North RA (2006) Vesicular release of ATP at central synapses. Pflugers Arch Eur J Physiol 452:589–597

    CAS  Google Scholar 

  • Parkinson FE, Xiong W, Zamzow CR (2005) Astrocytes and neurons: different roles in regulating adenosine levels. Neurol Res 27:153–160

    CAS  PubMed  Google Scholar 

  • Pascual O, Casper KB, Kubera C, Zhang J, Revilla-Sanchez R, Sul JY, Takano H, Moss SJ, McCarthy K, Haydon PG (2005) Astrocytic purinergic signaling coordinates synaptic networks. Science 310:113–116

    CAS  PubMed  Google Scholar 

  • Peakman MC, Hill SJ (1994) Adenosine A2B-receptor-mediated cyclic AMP accumulation in primary rat astrocytes. Br J Pharmacol 111:191–198

    CAS  PubMed  Google Scholar 

  • Ralevic V, Burnstock G (1998) Receptors for purines and pyrimidines. Pharmacol Rev 50:413–492

    CAS  PubMed  Google Scholar 

  • Rezin GT, Amboni G, Zugno AI, Quevedo J, Streck EL (2009) Mitochondrial dysfunction and psychiatric disorders. Neurochem Res 34:1021–1029

    CAS  PubMed  Google Scholar 

  • Rho JM, Kim DW, Robbins CA, Anderson GD, Schwartzkroin PA (1999) Age-dependent differences in flurothyl seizure sensitivity in mice treated with a ketogenic diet. Epilepsy Res 37:233–240

    CAS  PubMed  Google Scholar 

  • Rosenberg PA, Knowles R, Knowles KP, Li Y (1994) Beta-adrenergic receptor-mediated regulation of extracellular adenosine in cerebral cortex in culture. J Neurosci 14:2953–2965

    CAS  PubMed  Google Scholar 

  • Rosin DL, Hettinger BD, Lee A, Linden J (2003) Anatomy of adenosine A2A receptors in brain: morphological substrates for integration of striatal function. Neurology 61:S12–18

    CAS  PubMed  Google Scholar 

  • Rossi DJ, Oshima T, Attwell D (2000) Glutamate release in severe brain ischaemia is mainly by reversed uptake. Nature 403:316–321

    CAS  PubMed  Google Scholar 

  • Rudolphi KA, Schubert P, Parkinson FE, Fredholm BB (1992) Adenosine and brain ischemia. Cerebrovasc Brain Metab Rev 4:346–369

    CAS  PubMed  Google Scholar 

  • Sas K, Robotka H, Toldi J, Vécsei L (2007) Mitochondria, metabolic disturbances, oxidative stress and the kynurenine system, with focus on neurodegenerative disorders. J Neurol Sci 257:221–239

    CAS  PubMed  Google Scholar 

  • Schock SC, Leblanc D, Hakim AM, Thompson CS (2008) ATP release by way of connexin 36 hemichannels mediates ischemic tolerance in vitro. Biochem Biophys Res Commun 368:138–144

    CAS  PubMed  Google Scholar 

  • Schulte G, Fredholm BB (2003) Signalling from adenosine receptors to mitogen-activated protein kinases. Cell Signal 15:813–827

    CAS  PubMed  Google Scholar 

  • Sebastião AM, de Mendonca A, Moreira T, Ribeiro JA (2001) Activation of synaptic NMDA receptors by action potential-dependent release of transmitter during hypoxia impairs recovery of synaptic transmission on reoxygenation. J Neurosci 21:8564–8571

    PubMed  Google Scholar 

  • Signoretti S, Marmarou A, Tavazzi B, Lazzarino G, Beaumont A, Vagnozzi R (2001) N-Acetylaspartate reduction as a measure of injury severity and mitochondrial dysfunction following diffuse traumatic brain injury. J Neurotrauma 18:977–991

    CAS  PubMed  Google Scholar 

  • Stone TW (2002) Purines and neuroprotection. Adv Exp Med Biol 513:249–280

    CAS  PubMed  Google Scholar 

  • Stout CE, Costantin JL, Naus CC, Charles AC (2002) Intercellular calcium signaling in astrocytes via ATP release through connexin hemichannels. J Biol Chem 277:10482–10488

    CAS  PubMed  Google Scholar 

  • Sweeney MI (1996) Adenosine release and uptake in cerebellar granule neurons both occur via an equilibrative nucleoside carrier that is modulated by G proteins. J Neurochem 67:81–88

    CAS  PubMed  Google Scholar 

  • Thompson RJ, Zhou N, MacVicar BA (2006) Ischemia opens neuronal gap junction hemichannels. Science 312:924–927

    CAS  PubMed  Google Scholar 

  • Thompson SM, Haas HL, Gähwiler BH (1992) Comparison of the actions of adenosine at pre- and postsynaptic receptors in the rat hippocampus in vitro. J Physiol 451:347–363

    CAS  PubMed  Google Scholar 

  • Uhlemann ER, Neims AH (1972) Anticonvulsant properties of the ketogenic diet in mice. J Pharmacol Exp Ther 180:231–238

    CAS  PubMed  Google Scholar 

  • Wardas J (2002) Neuroprotective role of adenosine in the CNS. Pol J Pharmacol 54:313–326

    CAS  PubMed  Google Scholar 

  • Wilder RM (1921) The effects of ketonemia on the course of epilepsy. Mayo Clin Bull 2:307–308

    Google Scholar 

  • Zhang L, Krnjević K (1993) Whole-cell recording of anoxic effects on hippocampal neurons in slices. J Neurophysiol 69:118–127

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We acknowledge the support of Grant-in Aid for Scientific Research (KAKENHI) for Young Scientists (B) (No. 23790303 to M.K.Jr.), Takeda Science Foundation (to M.K.Jr.) and of the National Institute of Neurological Disease and Stroke (No. NS-065446 to D.N.R.).

Author information

Authors and Affiliations

  1. Department of Pharmacology, Jikei University School of Medicine, 3-25-8 Nishi-shimbashi, Minato-ku, Tokyo, 105-8461, Japan

    Masahito Kawamura Jr.

  2. Neuroscience Program and Department of Psychology, Trinity College, 300 Summit St, Hartford, CT, 06106, USA

    David N. Ruskin

Authors
  1. Masahito Kawamura Jr.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. David N. Ruskin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Masahito Kawamura Jr. .

Editor information

Editors and Affiliations

  1. Trinity College, 300 Summit Street, LSC 208, Hartford, 06106, USA

    Susan Masino

  2. Legacy Research Institute, Portland, OR,, 1225 NE 2nd Avenue, Portland, 97232, USA

    Detlev Boison

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media New York

About this chapter

Cite this chapter

Kawamura, M., Ruskin, D.N. (2013). Adenosine and Autocrine Metabolic Regulation of Neuronal Activity. In: Masino, S., Boison, D. (eds) Adenosine. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3903-5_4

Download citation

Publish with us

Policies and ethics

Search

Navigation