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The Role of Adenosine in Central Neuromodulation

  • Chapter
Regulatory Function of Adenosine

Part of the book series: Developments in Pharmacology ((DIPH,volume 2))

Abstract

The last decade has witnessed an enormous expansion of the research commitment into the actions of adenosine and its nucleotides on nerve and muscle cells. Interest in adenosine is not, however, a new phenomenon, and over fifty years have elapsed since the first observations of the actions of adenosine and adenosine 5’-monophosphate (AMP) on smooth and cardiac muscles [1]. The intervening years have seen a continuing interest in the peripheral actions of adenosine and its nucleotides, with the publication of an important monograph, Biological Actions of the Adenosine Nucleotides [2] in 1950. This text described the actions of adenine nucleotides and related purines on the cardiovascular and respiratory systems and clearly enunciated some of the structural requirements necessary for activation of purinergic receptors. The modern era of research on adenosine was initiated by the hypothesis, proposed by Burnstock and his colleagues [3], that adenosine 5’-triphosphate (A TP) is the transmitter released from so-called purinergic nerves, which form a third division of the autonomic nervous system. The hypothesis itself and the supporting data were elegantly outlined in a subsequent review [4]. It is curious that, although the status of the purinergic hypothesis remains somewhat uncertain, at least in the form in which it was originally presented, there has been widespread acceptance of the concept of adenosinergic modulation of transmitter release in both the central and peripheral nervous systems.

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References

  1. Drury AN, Szent-Györgyi A: The physiological activity of adenine compounds with especial reference to their action upon the mammalian heart. J Physiol (Lond) 68: 213-237, 1928.

    Google Scholar 

  2. Green HN, Stoner HB: Biological Actiolls of the Adellille Nucleotides. London, H.K. Lewis and Co., 1950.

    Google Scholar 

  3. Burnstock G, Campbell G, Satchell D, Smythe D: Evidence that adenosine triphosphate or a related nucleotide is the transmitter substance released by non-adrenergic inhibitory nerves in the gut. Br J Pharmacal 40: 668-688, 1970.

    CAS  Google Scholar 

  4. Burnstock G: Purinergic nerves. Phannacol Rev 24: 509-581, 1972.

    CAS  Google Scholar 

  5. Burnstock G: A basis for distinguishing two types of purinergic receptor, in Bolis L, Straub RW (eds): Cell Membralle Receptors for Drugs and Hormolles: A Multidisciplillary Approach. New York, Raven Press, 1978, pp 107–118.

    Google Scholar 

  6. Fedan JS, Hogaboom GK, O’Donnell JP, Colby J, Westfall DP: Contribution by purines to the neurogenic response of the vas deferens of the guinea pig. EurJ Pharmacol 69: 41-53, 1981.

    Article  CAS  Google Scholar 

  7. Brown CM, Burnstock G: The structural confirmation of the polyphosphate chain of the ATP molecule is critical for its promotion of prostaglandin biosynthesis. Eur J Pharmacal 69: 81-86, 1981.

    Article  CAS  Google Scholar 

  8. Van Calker D, Muller M, Hamprecht B: Adenosine regulates via two different types of receptors, the accumulation of cyclic AMP in cultured brain cells. J Neuroehem 33: 999-1005, 1979.

    Article  Google Scholar 

  9. Cooper DMF, Londos C, Rodbell M: Adenosine receptor-mediated inhibition of rat cerebral cortical adenylate cyclase by a GTP-dependent process. Mol Pharmacal 18: 598-601, 1980.

    CAS  Google Scholar 

  10. Paton DM: Structure-activity relations for presynaptic inhibition of noradrenergic and cholinergic transmission by adenosine: evidence for action on A1 receptors. J Auton Pharmacal 1: 287-290, 1981.

    Article  CAS  Google Scholar 

  11. Reddington M, Lee KS, Schubert P: An A,-adenosine receptor, characterized by [3H] cyclohexyl adenosine binding, mediates the depression on evoked potentials in a rat hippocampal slice preparation. Neurosci Lett 28: 275-279, 1982.

    Article  PubMed  CAS  Google Scholar 

  12. Brown CM, Collis MG: Evidence for an Ra purine receptor in the guinea pig trachealis muscle. Br J Pharmacol 75: 157P, 1982 (abst).

    Google Scholar 

  13. Phillis JW, Wu PH: The role of adenosine and its nucleotides in central synaptic transmission. Prog Neurobiol 16: 187-239, 1981.

    Article  PubMed  CAS  Google Scholar 

  14. Wu, PH, Phillis JW: Distribution and release of adenosine triphosphate in rat brain. Neuroehem Res 3: 563-571, 1978.

    Article  CAS  Google Scholar 

  15. Wu PH, Moore KC, Phillis JW: Topographical distribution of ATP in rat brain. Experientia 35: 881-883, 1979.

    Article  PubMed  CAS  Google Scholar 

  16. Gharib A, Sarda N, Chabannes B, Cronenberger L, Pacheco H: The regional concentrations of S-adenosyl-L-methionine, S-adenosyl-L-homocysteine, and adenosine in rat brain. J Neuroehem 38: 810-815, 1982.

    Article  CAS  Google Scholar 

  17. Holton P: The liberation of adenosine triphosphate on antidromic stimulation of sensory nerves. J Physiol (Lond) 145: 494-504, 1959.

    CAS  Google Scholar 

  18. Silinsky EM: On the association between transmitter secretion and the release of adenine nucleotides from mammalian motor nerve terminals. J Physiol (Lond) 247: 145-162, 1982.

    Google Scholar 

  19. Maire JC, Medilanski J, Straub RW: Uptake of adenosine and release of adenine derivatives in mammalian non-myelinated nerve fibres at rest and during activity. J Physiol 323: 589-602, 1982.

    PubMed  CAS  Google Scholar 

  20. Pull I, McIlwain H: Output of [14C] adenine nucleotides and their derivatives from cerebral tissues. Bioehem J 136: 893-901, 1973.

    CAS  Google Scholar 

  21. Daval JL, Barberis C, Gayet J: Release of [14C] adenosine derivatives from superfused synaptosome preparations: Effects of depolarizing agents and metabolic inhibitors. Brain Res 181: 161-174, 1980.

    Article  PubMed  CAS  Google Scholar 

  22. Bender AS, Wu PH, Phillis JW: The rapid uptake and release of [3H] adenosine by rat cerebral cortical synaptosomes. J Neuroehem 36: 651-660, 1981.

    Article  CAS  Google Scholar 

  23. Fredholm BB, Hedqvist P: Modulation of neurotransmission by purine nucleotides and nucleosides. Bioehem Pharmacol 29: 1635-1643, 1980.

    Article  CAS  Google Scholar 

  24. Sulakhe PV, Phillis JW: The release of [3H] adenosine and its derivatives from cat sensorimotor cortex. Life Sci 17: 551-556, 1975.

    Article  PubMed  CAS  Google Scholar 

  25. Phillis JW, Jiang ZG, Chelack BJ, Wu PH: The effect of morphine on purine and acetylcholine release from rat cerebral cortex: Evidence for a purinergic component in morphine’s action. Pharmacol Bioehem Behav 13: 421-427, 1980.

    Article  CAS  Google Scholar 

  26. Jhamandas K, Dumbrille A: Regional release of [3H] adenosine derivatives from rat brain in vivo: Effect of excitatory amino acids, opiate agonists, and benzodiazepines. Can J Physiol Pharmacol 58: 1262-1278, 1980.

    PubMed  CAS  Google Scholar 

  27. Berne RM, Rubio R, Curnish R: Release of adenosine from ischemic brain. Cire Res 25: 262-272, 1974.

    Google Scholar 

  28. Winn HR, Rubio R, Berne RM: Brain adenosine production in the rat during 60 seconds of ischemia. Cire Res 45: 485-492, 1979.

    Google Scholar 

  29. Winn HR, Rubio R, Berne RM: Brain adenosine concentration during hypoxia in rats. Am J Physiol 241: H235–H242, 1981.

    PubMed  CAS  Google Scholar 

  30. Winn HR, Welsh JE, Rubio R, Berne RM: Brain adenosine production in rat during sustained alteration in systemic blood pressure. Am J Physiol 239: H636–H641, 1980.

    PubMed  CAS  Google Scholar 

  31. Zetterstriim 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 29: 111-115, 1982.

    Article  Google Scholar 

  32. Kuroda Y: Physiological roles of adenosine derivatives which are released during neurotransmission in mammalian brain. J Physiol (Paris) 74: 463-470, 1978.

    CAS  Google Scholar 

  33. Katsuragi T, Su C: Purine release from vascular adrenergic nerves by high potassium and a calcium ionophore, A-23187. J Pharmacal Exp Ther 215: 685-690, 1980.

    CAS  Google Scholar 

  34. Israel M, Lesbats B, Meunier FM, Stinnakre J: Postsynaptic release of adenosine triphosphate induced by single impulse transmitter action. Proc R Soc Lond [Biol] 193: 461-468, 1976.

    Article  CAS  Google Scholar 

  35. Forrester T, Lind AR: Identification of adenosine triphosphate in human plasma and the concentration in the venous effluent of forearm muscles before, during and after sustained contractions. J Physiol 204: 347-364, 1969.

    PubMed  CAS  Google Scholar 

  36. Phillis JW, Wu PH: Roles of adenosine and adenine nucleotides in the C.N.S., in Daly JW, Kuroda Y, Phillis JW, Shimizu H, Ui M (eds): Physiology and Pharmacology of Adenosine Derivatives. New York, Raven Press, 1983, pp. 219–236.

    Google Scholar 

  37. Phillis JW, Edstrom JP, Kostopoulos GK, Kirkpatrick JR: Effects of adenosine and adenine nucleotides on synaptic transmission in the cerebral cortex. Can J Physiol Pharmacol 57: 1289-1312, 1979.

    Article  PubMed  CAS  Google Scholar 

  38. Feldberg W, Sherwood SL: Injections of drugs into the lateral ventricle of the cat. J Physiol (Lond) 123: 148-167, 1954.

    CAS  Google Scholar 

  39. Buday PV, Carr CJ, Miya TS: A pharmacologic study of some nucleosides and nucleotides. J Pharm PharmacoI 13: 290-299, 1961.

    Article  CAS  Google Scholar 

  40. Haulica I, Ababei L, Brănisteanu D, Topoliceanu F: Preliminary data on the possible hypnogenic role of adenosine. J Neurochem 21: 1019-1020, 1973.

    Article  PubMed  CAS  Google Scholar 

  41. Yarbrough GG, McGuffin-Clineschmidt JC: In vivo behavioral assessment of central nervous system purinergic receptors. Eur J Pharmacol 76: 137-144, 1981.

    Article  PubMed  CAS  Google Scholar 

  42. Daly JW, Bruns RF, Snyder SH: Adenosine receptors in the central nervous system: Relationship to the central actions of methylxanthines. Life Sci 28: 2083-2097, 1981.

    Article  PubMed  CAS  Google Scholar 

  43. Kostopoulos GK, Phillis JW: Purinergic depression of neurons in different areas of the rat brain. Exp Neurol 55: 719-724, 1977.

    Article  PubMed  CAS  Google Scholar 

  44. Phillis JW: Evidence for an Arlike adenosine receptor on cerebral cortical neurons. J Pharm Pharmacol 34: 453-454, 1982.

    Article  PubMed  CAS  Google Scholar 

  45. Smellie FW, Daly JW, Dunwiddie TV, Hoffer BJ: The dextro and levorotatory isomers ofNphenylisopropyladenosine: Stereospecific effects on cyclic AMP-formation and evoked synaptic responses in brain slices. Life Sci 25: 1739-1748, 1979.

    Article  PubMed  CAS  Google Scholar 

  46. Reddington M, Schubert P: Parallel investigations of the effects of adenosine on evoked potentials and cyclic AMP accumulation in hippocampal slices of the rat. Neurosci Lett 14: 37-42, 1979.

    Article  PubMed  CAS  Google Scholar 

  47. Finnerty, FA, Witkin L, Fazekas JF: Cerebral haemodynamics during cerebral ischemia induced by acute hypotension. J Clin Invest 33: 1227-1232, 1954.

    Article  PubMed  Google Scholar 

  48. Lassen NA: Cerebral blood flow and oxygen consumption in man. Physiol Rev 39: 183-238, 1959.

    PubMed  CAS  Google Scholar 

  49. Harper AM: Autoregulation of cerebral blood flow: Influence of the arterial blood pressure on the blood flow through the cerebral cortex. J Neurol Neurosurg Psychiatry 29: 398-403, 1966.

    Article  PubMed  CAS  Google Scholar 

  50. Fitch W, Ferguson GG, Sengupta D, Garisi J, Harper AM: Autoregulation of cerebral blood flow during controlled hypotension in baboons. J Neurol Neurosurg Psychiatry 39: 1014-1022, 1976.

    Article  PubMed  CAS  Google Scholar 

  51. Vizi ES: Presynaptic modulation of neurochemical transmission. Prog Neurobiol 12: 181-290, 1979.

    Article  PubMed  CAS  Google Scholar 

  52. Lekić D: Presynaptic depression of synaptic response of Renshaw cells by adenosine 5′monophosphate. Can J Physiol Pharmacol 55: 1391-1393, 1977.

    Article  PubMed  Google Scholar 

  53. Jhamandas K, Sawynok J: Methylxanthine antagonism of opiate and purine effects on the release of acetylcholine, in Kosterlitz HW (ed): Opiates and Endogenous Opioid Peptides. Amsterdam, Elsevier North-Holland, 1976, pp 161–168.

    Google Scholar 

  54. Phillis JW, Siemens RK, Wu PH: Effects of diazepam on adenosine and acetylcholine release from rat cerebral cortex: Further evidence for a purinergic mechanism in action of diazepam. Br J Pharmacol 70: 341-348, 1980.

    CAS  Google Scholar 

  55. Taylor DA, Stone TW: The action of adenosine on noradrenergic neuronal inhibition induced by stimulation of locus coeruleus. Brain Res 183: 367-376, 1980.

    Article  PubMed  CAS  Google Scholar 

  56. Harms HH, Wardeh G, Mulder AH: Adenosine modulates depolarization-induced release of 3H-noradrenaline from slices of rat brain neocortex. Eur J Pharmacol 49: 305-308, 1978.

    Article  PubMed  CAS  Google Scholar 

  57. Harms HH, Wardeh G, Mulder AH: Effects of adenosine on depolarization-induced release of various radio labelled neurotransmitters from slices of rat corpus striatum. Neuropharmacology 18: 577-580, 1979.

    Article  PubMed  CAS  Google Scholar 

  58. Michaelis ML, Michaelis EK, Myers SL: Adenosine modulation of synaptosomal dopamine release. Life Sci 24: 2083-2092, 1979.

    Article  PubMed  CAS  Google Scholar 

  59. Hollins C, Stone TW: Adenosine inhibition of γ-aminobutyric acid release from slices of rat cerebral cortex. Br J Pharmacol 69: 107-112, 1980.

    PubMed  CAS  Google Scholar 

  60. Ribeiro JA: The decrease of neuromuscular transmission by adenosine depends on previous neuromuscular depression. Arch Int Pharmacol 255: 59-67, 1982.

    CAS  Google Scholar 

  61. Ribeiro JA, Sa-Almeida AM, Namorado JM: Adenosine and adenosine triphosphate decrease 45Ca uptake by synaptosomes stimulated by potassium. Biochem Pharmacol 28: 1297-1300, 1979.

    Article  PubMed  CAS  Google Scholar 

  62. Ginsborg BL, Hirst GDS: The effect of adenosine on the release of transmitter from the phrenic nerve of the rat. J Physiol (Lond) 224: 629-645, 1972.

    CAS  Google Scholar 

  63. Branisteanu DD, Haulica ID, Proca B, Nitue BG: Adenosine effects upon transmitter release parameters in the Mg2+ -paralyzed neuromuscular junction offrog. Naunyn Schmiedebergs Arch Pharmacol 308: 273-279, 1979.

    Article  PubMed  CAS  Google Scholar 

  64. Wu PH, Phillis JW, Thierry DL: Adenosine receptor agonists inhibit K+ -evoked Ca2+ uptake by rat brain cortical synaptosomes. J Neurochem 39: 700-708, 1982.

    Article  PubMed  CAS  Google Scholar 

  65. Henon BK, Turner DK and McAfee DA: Adenosine receptors: Electrophysiological actions at pre- and postsynaptic sites on mammalian neurons. Soc Neurosci Abstr 6: 257, 1980.

    Google Scholar 

  66. Schrader J, Rubio R, Berne RM: Inhibition of slow action potentials of guinea pig atrial muscle by adenosine: A possible effect on Ca++ influx. J Mol Cell Cardiol 7: 427-433, 1975.

    Article  PubMed  CAS  Google Scholar 

  67. Hartzell HC: Adenosine receptors in frog sinus venosus: Slow inhibitory potentials produced by adenine compounds and acetylcholine. J Physiol (Lond) 293: 23-49, 1979.

    CAS  Google Scholar 

  68. Hutter OF, Rankin AC: Increase by adenosine and adenine nudeotides in potassium permeability of sinus venosus of tortoise heart. J Physiol, 1982 (in press).

    Google Scholar 

  69. Jager LP: The effect of catecholamines and ATP on the smooth muscle cell membrane of the guinea pig taenia coli. EurJ Pharmacol 25: 372-382, 1974.

    Article  CAS  Google Scholar 

  70. Maas AJJ, Den Hertog A, Ras R, Van Der Akker J: The action of apamin on guinea pig taenia caeci. Europ J Pharmacol 67: 265-274, 1980.

    Article  CAS  Google Scholar 

  71. Den Hertog, A: Calcium and the action of adrenaline, adenosine triphosphate and carbachol on guinea pig taenia caeci. J Physiol 325: 423-439, 1982.

    Google Scholar 

  72. Okada Y, Saito M: Inhibitory action of adenosine, 5-HT (serotonin) and GABA (γ-aminobutyric acid) on the postsynaptic potential (PSP) of slices from olfactory cortex and superior colliculus in correlation to the level of cyclic AMP. Brain Res 160: 368-371, 1979.

    Article  PubMed  CAS  Google Scholar 

  73. Phillis JW, Wu PH: The effect of various centrally active drugs on adenosine uptake by the central nervous system. Comp Biochem Physiol [C] 72C:179-187, 1982.

    Article  CAS  Google Scholar 

  74. Sugar O, Gerard R: Anoxia and brain potentials. J Neurophysiol 1: 558-572, 1938.

    Google Scholar 

  75. Grossman RG, Williams VF: Electrical activity and ultrastructure of cortical neurons and synapses in ischemia, in Brierley JB, Meldrum BA (eds): Brain Hypoxia. London, W. Heinemann, 1971, pp 61–75.

    Google Scholar 

  76. White BC, Gadzinski DS, Hoehner PJ, Krome C, Hoehner T, White JD, Trombley JH: Effect of flunarizine on canine cerebral cortical blood flow and vascular resistance post cardiac arrest. Ann Emerg Med 11: 119-126, 1982.

    Article  PubMed  CAS  Google Scholar 

  77. Hallenbeck JM, Furlow TW: Prostaglandin 12 and indomethacin prevent impairment of postischemic brain reperfusion in the dog. Stroke 10: 629-637, 1979.

    Article  PubMed  CAS  Google Scholar 

  78. Phillis JW, Wu PH: Indomethacin, ibuprofen and meclofenamate inhibit adenosine uptake by rat brain synaptosomes. Eur J Pharmacol 72: 139–140, 1981.

    Article  PubMed  CAS  Google Scholar 

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Authors
  1. John W. Phillis
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  2. Peter H. Wu
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Editors and Affiliations

  1. Department of Physiology, University of Virginia School of Medicine, Charlottesville, Virginia, USA

    Robert M. Berne  & Rafael Rubio  & 

  2. Department of Pharmacology, University of Virginia School of Medicine, Charlottesville, Virginia, USA

    Theodore W. Rall

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© 1983 Martinus Nijhoff Publishers, The Hague

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Phillis, J.W., Wu, P.H. (1983). The Role of Adenosine in Central Neuromodulation. In: Berne, R.M., Rall, T.W., Rubio, R. (eds) Regulatory Function of Adenosine. Developments in Pharmacology, vol 2. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-3909-0_26

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  • DOI: https://doi.org/10.1007/978-1-4613-3909-0_26

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-3911-3

  • Online ISBN: 978-1-4613-3909-0

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