Release and actions of adenosine in the central nervous system
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Abstract
Adenosine is released from active neurons into the extracellular fluid at a concentration of about 1μmol/l. Neither the precise cellular origin nor the biochemical form of release has been firmly established, though the nucleotide is probably released partly directly, as a result of raised intracellular levels, and partly as nucleotides, which are subsequently hydrolysed. Once in the extracellular medium, adenosine markedly inhibits the release of excitatory neurotransmitters and modulatory peptides and has direct inhibitory effects on postsynaptic excitability via A1 receptors. A population of A2 receptors may mediate depolarization and enhanced transmitter release. Adenosine also modulates neuronal sensitivity to acetylcholine and catecholarnines, all these effects probably contributing to the behavioural changes observed in conscious animals. As a result of their many actions, adenosine analogues are being intensively investigated for use as anticonvulsant, anxiolytic, and neuroprotective agents.
Keywords
Adenosine Central nervous system Interactions Neural transmission Neurosecretary systems Hippocampus Nucleosides Purines Receptors, purinergic SynapsesPreview
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References
- 1.Zetterstrom T, Vernet L, Ungerstedt U, Tossman U, Jonzon B, Fredholm BB. Purine levels in the intact rat brain. Studies with an implanted perfused hollow fibre. Neurosci Lett 1982;29:111–5.PubMedGoogle Scholar
- 2.Chen Y, Graham DI, Stone TW, Daval JL, Barberis C. Release of radiolabeled adenosine from perfused synaptosome beds. Biochem Pharmacol 1992;30:2559–67.Google Scholar
- 3.During MJ, Spencer DD. Adenosine: a potential mediator of seizure arrest and postictal refractoriness. Ann Neurol 1992;32:618–24.PubMedGoogle Scholar
- 4.Rehncrona S, Siesjo BK, Westerberg E. Adenosine and cyclic AMP in cerebral cortex of rats in hypoxia, status epilepticus and hypercapnia. Acta Physiol Scand 1978;104:453–63.PubMedGoogle Scholar
- 5.Winn HR, Rubio R, Berne RM. Brain adenosine concentration during hypoxia in rats. Am J Physiol 1981;241:H235–42.PubMedGoogle Scholar
- 6.Hoehn K, White TD. NMDA, kainate and quisqualate release endogenous adenosine from rat cortical slices. Neuroscience 1990;39:441–50.PubMedGoogle Scholar
- 7.Meghji P. Adenosine production and metabolism. In: Stone TW, editor. Adenosine in the nervous system. London: Academic Press, 1991:25–42.Google Scholar
- 8.Stone TW, Newby AC, Lloyd HGE. Adenosine release. In: Williams M, editor. Adenosine and adenosine receptors. New York: Humana Press, 1990:173–223.Google Scholar
- 9.Richardson PJ. Presynaptic distribution of the cholinergic specific antigen chol-1 and 5′-nucleotidase in cat brain as determined by complement-mediated release of neurotransmitters. J Neurochem 1983;41:640–8.PubMedGoogle Scholar
- 10.Grondal EJM, Janetzko A, Zimmerman H. Monospecific antiserum against 5′-nucleotidase fromTorpedo electric organ: immunocytochemical distribution of the enzyme and its association with Schwann cell membranes. Neuroscience 1988;24:351–63.PubMedGoogle Scholar
- 11.Kreutzberg GW, Heymann D, Reddington M. 5′-Nudeotidase in the nervous system. In: Kreutzberg GW, Reddington M, Zimmerman H, editors. Cellular biology of ecto-enzymes. Berlin: Springer-Verlag, 1986:148–75.Google Scholar
- 12.Gordon JL. Extracellular ATP: effects, sources, and fate. Biochem J 1986;233:309–19.PubMedGoogle Scholar
- 13.Pearson JD. Ectonucleotidases. Measurement of activities and use of inhibitors. Methods Pharmacol 1985;6:83–108.Google Scholar
- 14.Meghji P, Tuttle JB, Rubio R. Adenosine formation and release by embryonic chick neurones and ganglia. J Neurochem 1989;53:1852–60.PubMedGoogle Scholar
- 15.Pons F, Bruns RF, Daly JW. Depolarization-evoked accumulation of cAMP in brain slices: the requisite intermediate adenosine is not derived from hydrolysis of released ATP. J Neurochem 1980;34:1319–23.PubMedGoogle Scholar
- 16.Daval JL, Barberis C, Gayet J. Release of adenosine derivatives from superfused synaptosome preparations: effects of depolarising agents and metabolic inhibitors. Brain Res 1980;181:161–74.PubMedGoogle Scholar
- 17.Jonzon B, Fredholm BB. Release of purines, noradrenaline and GABA from rat hippocampal slices by field stimulation. J Neurochem 1985;44:217–24.PubMedGoogle Scholar
- 18.Richardson PJ, Brown SJ, Bailyes EM, Luzio JP. Ecto-enzymes control adenosine modulation of immunoisolated cholinergic synapses. Nature 1987;327:232–4.PubMedGoogle Scholar
- 19.McIlwain H. Regulatory significance of the release and action of adenine derivatives in cerebral systems. Biochem Soc Symp 1972;36:69–85.PubMedGoogle Scholar
- 20.Hollins C, Stone TW. Characteristics of the release of adenosine from slices of rat cerebral cortex. J Physiol 1980;303:73–82.PubMedGoogle Scholar
- 21.Hollins C, Stone TW, Lloyd H. Neuronal (Na,K)-ATPase and the release of purines from mouse and rat cerebral cortex. Neurosci Lett 1980;20:217–21.PubMedGoogle Scholar
- 22.Lloyd HGE, Stone TW. Factors effecting the release of purines from mouse cerebral cortex: potassium removal and metabolic inhibitors. Biochem Pharmacol 1980;30:1239–43.Google Scholar
- 23.Stone TW, Hollins C, Lloyd H. Methylxanthines modulate adenosine release from slices of cerebral cortex. Brain Res 1981;207:421–31.PubMedGoogle Scholar
- 24.Lloyd HGE, Stone TW. A different time course of purine release from rat brain slices and synaptosomes. J Physiol 1983;340:57P-8P.Google Scholar
- 25.Fredholm BB, Vernet L. Morphine increases depolarisation induced purine release from hypothalamic synaptosomes. Acta Physiol Scand 1978;104:502–4.PubMedGoogle Scholar
- 26.Fredholm BB, Fried G, Hedqvist P. Origin of adenosine released from rat vas deferens by nerve stimulation. Eur J Pharmacol 1981;79:233–43.Google Scholar
- 27.Pull I, McIlwain H. Output of [14C]adenine nucleotides and their derivatives from cerebral tissues. Biochem J 1973;136:893–901.PubMedGoogle Scholar
- 28.Fredholm BB, Vernet L. Release of [3H] nucleotides from [3H]adenine labeled hypothalamic synaptosomes. Acta Physiol Scand 1979;106:97–107.PubMedGoogle Scholar
- 29.Wu PH, Moron M, Barraco R. Organic calcium channel blockers enhance [3H]purine release from rat brain cortical synaptosomes. Neurochem Res 1984;9:1019–31.PubMedGoogle Scholar
- 30.White TD. Release of ATP from a synaptosomal preparation by elevated extracellular potassium and by veratridine. J Neurochem 1978;30:329–36.PubMedGoogle Scholar
- 31.Wyllie MG, Gilbert JC. Exocytotic release of noradrenaline from synaptosomes. Biochem Pharmacol 1980;29:1302–3.PubMedGoogle Scholar
- 32.White TD, Downie JW, Leslie RA. Characteristics of potassium and veratridine induced release of ATP from synaptosomes prepared for dorsal and ventral spinal cord. Brain Res 1985;334:372–4.PubMedGoogle Scholar
- 33.Potter P, White TD. Release of adenosine 5′-triphosphate from synaptosomes from different regions of rat brain. Neuroscience 1980;5:1351–6.PubMedGoogle Scholar
- 34.White TD, Potter P, Wonnacott S. Depolarisation-induced release of ATP from cortical synaptosomes is not associated with acetylcholine release. J Neurochem 1980;34:1109–12.PubMedGoogle Scholar
- 35.Potter P, White TD. Lack of effect of 6-hydroxydopamine pretreatment on depolarisation-induced release of ATP from rat brain synaptosomes. Eur J Pharmacol 1982;80:143–7.PubMedGoogle Scholar
- 36.Schubert P, Komp W, Kreutzberg GW. Correlation of 5′-nucleotidase activity and selective transneuronal transfer of adenosine in the hippocampus. Brain Res 1979;168:419–24.PubMedGoogle Scholar
- 37.Perkins MN, Stone TW.In vivo release of [3H]purines by quinolinic acid and related compounds. Br J Pharmacol 1983;80:263–7.PubMedGoogle Scholar
- 38.Sulakhe PV, Phillis JW. The release of [3H]adenosine and its derivatives from cat sensorimotor cortex. Life Sci 1975;17:551–6.PubMedGoogle Scholar
- 39.Jhamandas K, Dumbrille A. Regional release of [3H]adenosine derivatives from rat brainin vivo: effects of excitatory amino acids, opiate agonists and benzodiazepines. Can J Physiol Pharmacol 1980;58:1262–78.PubMedGoogle Scholar
- 40.Wu PH, Phillis JW. Distribution and release of adenosine triphosphate in rat brain. Neurochem Res 1978;3:563–71.PubMedGoogle Scholar
- 41.Barberis C, Guibert B, Daudet F, Charriere B, Leviel V.In vivo release of adenosine from cat basal ganglia — studies with a push pull cannula. Neurochem Int 1984;6:545–51.Google Scholar
- 42.Wojcik WJ, Neff NH. Location of adenosine release and adenosine A2 receptors to rat striatal neurons. Life Sci 1983;33:755–63.Google Scholar
- 43.Wu PH, Phillis JW, Yuen H. Morphine enhances the release of [3H]purines from rat brain cerebral cortical prisms. Pharmacol Biochem Behav 1982;17:749–55.PubMedGoogle Scholar
- 44.Stone TW. The effects of morphine and methionine-enkephalin on the release of purines from cerebral cortex slices of rats and mice. Br J Pharmacol 1981;74:171–6.PubMedGoogle Scholar
- 45.Phillis JW, Jiang ZG, Chelack BJ, Wu PH. Morphine enhances adenosine release from thein vivo rat cerebral cortex. Eur J Pharmacol 1979;65:97–100.Google Scholar
- 46.Stone TW. Actions of adenine dinucleotides on the vas deferens, guinea-pig taenia caeci and bladder. Eur J Pharmacol 1981;75:93–102.PubMedGoogle Scholar
- 47.Winn HR, Rubio R, Berne RM. Changes in brain adenosine during bicuculline-induced seizures in rats: effects of hypoxia and altered systemic blood pressure. Circ Res 1980;47:481–91.Google Scholar
- 48.Schrader J, Wahl M, Kuschinsky W, Kreutzberg GW. Increase of adenosine content in cerebral cortex of the cat during bicuculline-induced seizure. Pflugers Arch 1980;387:45–51.Google Scholar
- 49.Rubio R, Berne RM, Bockman EL, Curnish RR. Relationship between adenosine concentration and oxygen supply in rat brain. Am J Physiol 1975;228:1896–902.PubMedGoogle Scholar
- 50.Winn HR, Rubio R, Berne RM. Brain adenosine production during 60 seconds of ischaemia. Circ Res 1979;45:486–92.PubMedGoogle Scholar
- 51.Winn HR, Welsh JE, Rubio R, Berne RM. Brain adenosine production in rats during sustained alteration in systemic blood pressure. Am J Physiol 1980;239:H636–41.PubMedGoogle Scholar
- 52.Winn HR, Morii S, Weaver DD, Reed JC, Ngai AC, Berne RM. Changes in brain adenosine concentration during hypoglycemia and posthypoxic hyperemia. J Cereb Blood Flow Metabol 1983;3(Suppl 1):S449–50.Google Scholar
- 53.Stone TW. Adenosine and related compounds do not affect nerve terminal excitability in rat CNS. Brain Res 1980;182:198–200.PubMedGoogle Scholar
- 54.Creveling CR, McNeal ET, McCulloch DH, Daly JW. Membrane potentials in cell free preparations from guinea-pig cerebral cortex: effect of depolarizing agents and cyclic nucleotides. J Neurochem 1980;35:922–32.PubMedGoogle Scholar
- 55.Goodman RR, Snyder SH. Autoradiographic localization of adenosine receptors in rat brain using [3H]cyclohexyladenosine. J Neurosci 1982;2:1230–41.PubMedGoogle Scholar
- 56.Goodman RR, Kuhar MJ, Bester L, Snyder SH. Adenosine receptors: autoradiographic evidence for their location on axon terminals of excitatory neurones. Science 1983;220:967–8.PubMedGoogle Scholar
- 57.Hollins C, Stone TW. Adenosine inhibition of GABA release from slices of rat cerebral cortex. Br J Pharmacol 1980;69:107–12.PubMedGoogle Scholar
- 58.Jonzon B, Fredholm BB. Adenosine receptor mediated inhibition of noradrenaline release from slices of the rat hippocampus. Life Sci 1984;35:1971–9.PubMedGoogle Scholar
- 59.Lambert NA, Teyler TJ. Adenosine depresses excitatory but not fast inhibitory synaptic transmission in area CA1 of the rat hippocampus. Neurosci Lett 1991;122:50–2.PubMedGoogle Scholar
- 60.Thompson SM, Haas HL, Grahwiler BH. Comparison of the actions of adenosine at pre- and postsynaptic receptors in the rat hippocampusin vitro. J Physiol 1992;451:347–63.PubMedGoogle Scholar
- 61.Yoon K-W, Rothman SM. Adenosine inhibits excitatory but not inhibitory synaptic transmission in the hippocampus. J Neurosci 1991;11:1375–80.PubMedGoogle Scholar
- 62.Fredholm BB, Proctor W, Van der Ploeg I, Dunwiddie TV.In vivo pertussis toxin treatment attenuates some, but not all, adenosine A1 effects in slices of the rat hippocampus. Eur J Pharmacol 1989;172:249–62.PubMedGoogle Scholar
- 63.Bartrup JT, Stone TW. Interactions of adenosine and magnesium on rat hippocampal slices. Brain Res 1988;463:374–9.PubMedGoogle Scholar
- 64.Higgins MJ, Stone TW. Bicuculline-resistant paired pulse inhibition in the rat hippocampal slices. Br J Pharmacol 1993;109:1164–8.PubMedGoogle Scholar
- 65.Phillis JW, Kostopoulos GK, Limacher JM. Depression of corticospinal cells by various purines and pyrimidines. Can J Physiol Pharmacol 1974;52:1226–9.PubMedGoogle Scholar
- 66.Stone TW, Perkins MN. Adenine dinucleotide effects on rat cortical neurones. Brain Res 1981;229:241–6.PubMedGoogle Scholar
- 67.Stone TW, Cusack NJ. Absence of P2-purinoceptors in hippocampal pathways. Br J Pharmacol 1989;97:631–6.PubMedGoogle Scholar
- 68.Siggins GR, Schubert P. Adenosine depression of hippocampal neuronesin vitro: an intracellular study of dose-dependent actions of synaptic and membrane potentials. Neurosci Lett 1981;23:55–60.PubMedGoogle Scholar
- 69.Segal M. Intracellular analysis of a postsynaptic action of adenosine in the rat hippocampus. Eur J Pharmacol 1982;79:193–200.PubMedGoogle Scholar
- 70.Trussell LO, Jackson MB. Adenosine-activated potassium conductance in cultured striatal neurons. Proc Natl Acad Sci USA 1985;82:4857–60.PubMedGoogle Scholar
- 71.Greene RW, Haas HL. Adenosine actions on CA1 pyramidal neurones in rat hippocampal slices. J Physiol (Lond) 1985;366:119–27.Google Scholar
- 72.Haas HL. Histamine potentiates neuronal excitation by blocking a calcium-dependent potassium conductance. Agents Actions 1984;16:3–4.Google Scholar
- 73.Haas HL, Greene RW. Adenosine enhances after hyper-polarization and accommodation in hippocampal pyramidal cells. Pflügers Arch 1984;402:244–7.Google Scholar
- 74.Proctor W, Dunwiddie TV. Adenosine inhibits calcium spikes in hippocampal pyramidal neuronesin vitro. Neurosci Lett 1983;35:197–201.PubMedGoogle Scholar
- 75.Hosseinzadeh H, Stone TW. Apparent desensitisation to adenosine of hippocampal pyramidal cells. Br J Pharmacol 1993;109;75.Google Scholar
- 76.Sattin A, Rall TW. The effect of adenosine and adenine nucleotides on the cyclic AMP content of guinea-pig cerebral cortex slices. Mol Pharmacol 1970;6:13–23.PubMedGoogle Scholar
- 77.Long CJ, Stone TW. Effects of adenosine on adrenoceptor sensitivity in rat vas deferens. Eur J Pharmacol 1986;132:11–20.PubMedGoogle Scholar
- 78.Kennedy C, Burnstock G. ATP causes postjunctional potentiation of noradrenergic contractions in the portal vein of guinea-pig and rat. J Pharm Pharmacol 1986;38:307–9.PubMedGoogle Scholar
- 79.Taylor DA, Stone TW. The action of adenosine on noradrenergic neuronal inhibition induced by stimulation of locus coeruleus. Brain Res 1980;183:367–76.PubMedGoogle Scholar
- 80.Bijak M, Misgefd U, Muller W. Interaction of noradrenergic and cholinergic agonists with ligands increasing potassium conductance of guinea pig hippocampal neuronesin vitro. Eur J Neurosci 1991;3:473–9.PubMedGoogle Scholar
- 81.Ewald DA. Potentiation of postjunctional cholinergic sensitivity of rat diaphragm muscle by high-energy phosphate adenine nucleotides. J Membr Biol 1976;29:47–65.PubMedGoogle Scholar
- 82.Akasu T, Hirai K, Koketsu K. Increase of acetylcholine receptor sensitivity by ATP: a novel action of ATP on acetylcholine sensitivity. Br J Pharmacol 1981;74:505–7.PubMedGoogle Scholar
- 83.Gustafsson LE, Wiklund NP, Cederqvist B. Apparent enhancement of cholinergic transmission in rabbit bronchi via adenosine A2 receptors. Eur J Pharmacol 1986;120:179–85.PubMedGoogle Scholar
- 84.Brooks PA, Stone TW. Purine modulation of cholinomimetic responses in the rat hippocampal slice. Brain Res 1988;458:106–14.PubMedGoogle Scholar
- 85.Mally J, Connick JH, Stone TW. Theophylline down-regulates adenosine receptor function. Brain Res 1990;509:141–5.PubMedGoogle Scholar
- 86.Michaelis ML, Michaelis EK, Myers SL. Adenosine modulation of synaptosomal dopamine release. Life Sci 1979;24:2083–92.PubMedGoogle Scholar
- 87.Chowdhury M, Fillenz M. Presynaptic adenosineA 2 andN-methyl-D-aspartate receptors regulate dopamine synthesis in rat striatal synaptosomes. J Neurochem 1991;56:1783–8.PubMedGoogle Scholar
- 88.Ferré S, Fuxe K, von Euler G, Johansson B, Fredholm BB. Adenosine-dopamine interactions in the brain. Neuroscience 1992;51:501–12.PubMedGoogle Scholar
- 89.Schiffmann SN, Jacobs O, Vanderhaeghen JJ. (RDC8) is expressed by enkephalin but not by substance P neurons: anin situ hybridization histochemistry study. J Neurochem 1992;57:1062–7.Google Scholar
- 90.Ferré S, Herrera-Marschitz M, Grabowska-Andén M, Ungerstedt U, Casas M, Andén N-E. Postsynaptic dopamine/adenosine interaction: II. Postsynaptic dopamine agonism and adenosine antagonism of methylxanthines in short-term reserpinized mice. Eur J Pharmacol 1991;192:36–42.Google Scholar
- 91.Heffner TG, Wiley JN, Williams AE, Bruns RF, Coughenour LL, Downs DA. Comparison of the behavioural effects of adenosine agonists and dopamine antagonists in mice. Psychopharmacology 1989;98:31–7.PubMedGoogle Scholar
- 92.Stone TW. Purine receptors and their pharmacological potential. Adv Drug Res 1989;18:292–429.Google Scholar
- 93.Stone TW, Simmonds HA. Purines: basic and clinical aspects. Dordrecht: Kluwer Press, 1991.Google Scholar
- 94.Dragunow M. Purinergic mechanisms in epilepsy. Prog Neurobiol 1988;31:85–108.PubMedGoogle Scholar
- 95.Simpson RE, O'Regan MH, Perkins LM, Phillis JW. Excitatory amino acid release from the ischaemic rat cerebral cortex: effects of adenosine receptor agonists and antagonists. J Neurochem 1992;58:1683–90.PubMedGoogle Scholar
- 96.Cantor SL, Zornow MH, Miller LP, Yaksh TL. The effect of cyclohexyladenosine on the periischemic increases of hippocampal glutamate and glycine in the rabbit. J Neurochem 1992;59:1884–92.PubMedGoogle Scholar
- 97.Rudolphi KA, Keil M, Hinze HJ. Effect of theophylline on ischaemically induced hippocampal damage in Mongolian gerbils; a behavioural and histopathological study. J Cereb Blood Flow Metab 1987;7:74–81.PubMedGoogle Scholar
- 98.Von Lubitz DKEJ, Dambrosia JM, Redmond DJ. Protective effect of cyclohexyladenosine in treatment of cerebral ischaemia in gerbils. Neuroscience 1989;30:452–62.Google Scholar
- 99.MacGregor DG, Miller WJ, Stone TW. The neuroprotective action of R-PIA is mediated through a centrally located adenosine A1 receptor. Br J Pharmacol 1993;110:470–6.PubMedGoogle Scholar
- 100.Lau Y-S, Mourdian MM. Protection against acute MPTP-induced dopamine depletion in mice by adenosine A1 agonist. J Neurochem 1993;60:768–71.PubMedGoogle Scholar