Skip to main content
Log in

Purinergic transmission in the central nervous system

  • Invited Review
  • Published:
Pflügers Archiv Aims and scope Submit manuscript

Abstract

The adenosine 5′-triphosphate (ATP), discovered in 1929 by Karl Lohman, Cyrus Hartwell Fiske, and Yellagaprada SubbaRow, acts as an important extracellular signaling molecule. In the CNS, ATP can be released from synaptic terminals, either on its own or together with other neurotransmitters. After the release from the presynaptic terminals, ATP binds to a plethora of ionotropic and metabotropic receptors, which mediate its action as an excitatory neurotransmitter. Furthermore, ATP also acts as an important mediator in neuronal–glial communications because glial cells are endowed with numerous ATP receptors, which trigger Ca2+ signaling events and membrane currents in both macro and microglia. In addition, ATP can be released from astroglial cells, thereby acting as a mediator of glial–glial and glial–neuronal signaling.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Abbracchio MP, Burnstock G (1994) Purinoceptors: are there families of P2X and P2Y purinoceptors? Pharmacol Ther 64:445–475

    Article  PubMed  CAS  Google Scholar 

  2. Arcuino G, Lin JH, Takano T, Liu C, Jiang L, Gao Q, Kang J, Nedergaard M (2002) Intercellular calcium signaling mediated by point-source burst release of ATP. Proc Natl Acad Sci USA99:9840–9845

    Article  PubMed  CAS  Google Scholar 

  3. Bardoni R, Goldstein PA, Lee CJ, Gu JG, MacDermott AB (1997) ATP P2X receptors mediate fast synaptic transmission in the dorsal horn of the rat spinal cord. J Neurosci 17:5297–5304

    PubMed  CAS  Google Scholar 

  4. Barrera NP, Ormond SJ, Henderson RM, Murrell-Lagnado RD, Edwardson JM (2005) Atomic force microscopy imaging demonstrates that P2X2 receptors are trimers but that P2X6 receptor subunits do not oligomerize. J Biol Chem 280:10759–10765

    Article  PubMed  CAS  Google Scholar 

  5. Bezzi P, Gundersen V, Galbete JL, Seifert G, Steinhauser C, Pilati E, Volterra A (2004) Astrocytes contain a vesicular compartment that is competent for regulated exocytosis of glutamate. Nat Neurosci 7:613–620

    Article  PubMed  CAS  Google Scholar 

  6. Bodin P, Burnstock G (2001) Purinergic signalling: ATP release. Neurochem Res 26:959–969

    Article  PubMed  CAS  Google Scholar 

  7. Burnstock G (1972) Purinergic nerves. Pharmacol Rev 24:509–581

    PubMed  CAS  Google Scholar 

  8. Burnstock G (1978) A basis for distinguishing two types of purinergic receptor. In: Straub RW, Bolis L (eds) Cell membrane receptors for drugs and hormones: a multidisciplinary approach. Raven, New York, pp 107–118

    Google Scholar 

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

    PubMed  CAS  Google Scholar 

  10. Chaudry IH (1982) Does ATP cross the cell plasma membrane. Yale J Biol Med 55:1–10

    PubMed  CAS  Google Scholar 

  11. Cotrina ML, Lin JH, Lopez-Garcia JC, Naus CC, Nedergaard M (2000) ATP-mediated glia signaling. J Neurosci 20:2835–2844

    PubMed  CAS  Google Scholar 

  12. 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

    Article  PubMed  CAS  Google Scholar 

  13. Drury AN (1936) The physiological activity of nucleic acid and its derivatives. Physiol Rev 16:292–325

    CAS  Google Scholar 

  14. Drury AN, Szent-Györgyi A (1929) The physiological activity of adenine compounds with special reference to their action upon mammalian heart. J Physiol (London) 68:213–237

    CAS  Google Scholar 

  15. Dunn PM, Blakeley AG (1988) Suramin: a reversible P2-purinoceptor antagonist in the mouse vas deferens. Br J Pharmacol 93:243–245

    PubMed  CAS  Google Scholar 

  16. Edwards FA (1994) ATP receptors. Curr Opin Neurobiol 4:347–352

    Article  PubMed  CAS  Google Scholar 

  17. Edwards FA, Gibb AJ, Colquhoun D (1992) ATP receptor-mediated synaptic currents in the central nervous system. Nature 359:144–147

    Article  PubMed  CAS  Google Scholar 

  18. Edwards FA, Robertson SJ, Gibb AJ (1997) Properties of ATP receptor-mediated synaptic transmission in the rat medial habenula. Neuropharmacology 36:1253–1268

    Article  PubMed  CAS  Google Scholar 

  19. Evans RJ, Derkach V, Surprenant A (1992) ATP mediates fast synaptic transmission in mammalian neurons. Nature 357:503–505

    Article  PubMed  CAS  Google Scholar 

  20. Fellin T, Pozzan T, Carmignoto G (2006) Purinergic receptors mediate two distinct glutamate release pathways in hippocampal astrocytes. J Biol Chem 281:4274–4284

    Article  PubMed  CAS  Google Scholar 

  21. Fields RD, Stevens B (2000) ATP: an extracellular signaling molecule between neurons and glia. Trends Neurosci 23:625–633

    Article  PubMed  CAS  Google Scholar 

  22. Franke H, Grosche J, Schadlich H, Krugel U, Allgaier C, Illes P (2001) P2X receptor expression on astrocytes in the nucleus accumbens of rats. Neuroscience 108:421–429

    Article  PubMed  CAS  Google Scholar 

  23. Fiske CH, SubbaRow Y (1929) Phosphorous compounds of muscle and liver. Science 70:381–382

    Article  PubMed  CAS  Google Scholar 

  24. Giaume C, Venance L (1998) Intercellular calcium signaling and gap junctional communication in astrocytes. Glia 24:50–64

    Article  PubMed  CAS  Google Scholar 

  25. Glynn IM (1968) Membrane adenosine triphosphatase and cation transport. Br Med Bull 24:165–169

    PubMed  CAS  Google Scholar 

  26. Guthrie PB, Knappenberger J, Segal M, Bennett MV, Charles AC, Kater SB (1999) ATP released from astrocytes mediates glial calcium waves. J Neurosci 19:520–528

    PubMed  CAS  Google Scholar 

  27. Haas S, Brockhaus J, Verkhratsky A, Kettenmann H (1996) ATP-induced membrane currents in ameboid microglia acutely isolated from mouse brain slices. Neuroscience 75:257–261

    Article  PubMed  CAS  Google Scholar 

  28. Haydon PG (2001) GLIA: listening and talking to the synapse. Nat Rev Neurosci 2:185–193

    Article  PubMed  CAS  Google Scholar 

  29. Hoffmann A, Kann O, Ohlemeyer C, Hanisch UK, Kettenmann H (2003) Elevation of basal intracellular calcium as a central element in the activation of brain macrophages (microglia): suppression of receptor-evoked calcium signaling and control of release function. J Neurosci 23:4410–4419

    PubMed  CAS  Google Scholar 

  30. Holton P (1959) The liberation of adenosine triphosphate on antidromic stimulation of sensory nerves. J Physiol 145:494–504

    PubMed  CAS  Google Scholar 

  31. Illes P, Ribeiro JA (2004) Neuronal P2 receptors of the central nervous system. Curr Top Med Chem 4:831–838

    Article  PubMed  CAS  Google Scholar 

  32. Jahr CE, Jessell TM (1983) ATP excites a subpopulation of rat dorsal horn neurones. Nature 304:730–733

    Article  PubMed  CAS  Google Scholar 

  33. Jo YH, Role LW (2002) Coordinate release of ATP and GABA at in vitro synapses of lateral hypothalamic neurons. J Neurosci 22:4794–4804

    PubMed  CAS  Google Scholar 

  34. Jo YH, Schlichter R (1999) Synaptic corelease of ATP and GABA in cultured spinal neurons. Nat Neurosci 2:241–245

    Article  PubMed  CAS  Google Scholar 

  35. Khakh BS (2001) Molecular physiology of P2X receptors and ATP signalling at synapses. Nat Rev Neurosci 2:165–174

    Article  PubMed  CAS  Google Scholar 

  36. Kirischuk S, Moller T, Voitenko N, Kettenmann H, Verkhratsky A (1995) ATP-induced cytoplasmic calcium mobilization in Bergmann glial cells. J Neurosci 15:7861–7871

    PubMed  CAS  Google Scholar 

  37. Kirischuk S, Scherer J, Kettenmann H, Verkhratsky A (1995) Activation of P2-purinoreceptors triggered Ca2+ release from InsP3-sensitive internal stores in mammalian oligodendrocytes. J Physiol (London) 483(Pt 1):41–57

    CAS  Google Scholar 

  38. Kolb HA, Wakelam MJ (1983) Transmitter-like action of ATP on patched membranes of cultured myoblasts and myotubes. Nature 303:621–623

    Article  PubMed  CAS  Google Scholar 

  39. Krishtal OA, Marchenko SM, Pidoplichko VI (1983) Receptor for ATP in the membrane of mammalian sensory neurones. Neurosci Lett 35:41–45

    Article  PubMed  CAS  Google Scholar 

  40. Kukley M, Barden JA, Steinhauser C, Jabs R (2001) Distribution of P2X receptors on astrocytes in juvenile rat hippocampus. Glia 36:11–21

    Article  PubMed  CAS  Google Scholar 

  41. Lippman F (1941) Metabolic generation and utilization of phosphate bond energy. Enzymology 1:99

    Google Scholar 

  42. Lohman K (1929) Uber die Pyrophosphatfraktion im Muskel. Naturwissenschaften 17:624–625

    Google Scholar 

  43. Moller T, Kann O, Verkhratsky A, Kettenmann H (2000) Activation of mouse microglial cells affects P2 receptor signaling. Brain Res 853:49–59

    Article  PubMed  CAS  Google Scholar 

  44. Mori M, Heuss C, Gahwiler BH, Gerber U (2001) Fast synaptic transmission mediated by P2X receptors in CA3 pyramidal cells of rat hippocampal slice cultures. J Physiol 535:115–123

    Article  PubMed  CAS  Google Scholar 

  45. Newman EA (2003) New roles for astrocytes: regulation of synaptic transmission. Trends Neurosci 26:536–542

    Article  PubMed  CAS  Google Scholar 

  46. North RA (2002) Molecular physiology of P2X receptors. Physiol Rev 82:1013–1067

    PubMed  CAS  Google Scholar 

  47. Pankratov Y, Castro E, Miras-Portugal MT, Krishtal O (1998) A purinergic component of the excitatory postsynaptic current mediated by P2X receptors in the CA1 neurons of the rat hippocampus. Eur J Neurosci 10:3898–3902

    Article  PubMed  CAS  Google Scholar 

  48. Pankratov Y, Lalo U, Krishtal O, Verkhratsky A (2002) Ionotropic P2X purinoreceptors mediate synaptic transmission in rat pyramidal neurones of layer II/III of somato-sensory cortex. J Physiol 542:529–536

    Article  PubMed  CAS  Google Scholar 

  49. Pankratov Y, Lalo U, Krishtal O, Verkhratsky A (2003) P2X receptor-mediated excitatory synaptic currents in somatosensory cortex. Mol Cell Neurosci 24:842–849

    Article  PubMed  CAS  Google Scholar 

  50. 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

    Article  PubMed  CAS  Google Scholar 

  51. Raivich G (2005) Like cops on the beat: the active role of resting microglia. Trends Neurosci 28:571–573

    Article  PubMed  CAS  Google Scholar 

  52. Robertson SJ, Edwards FA (1998) ATP and glutamate are released from separate neurones in the rat medial habenula nucleus: frequency dependence and adenosine-mediated inhibition of release. J Physiol 508:691–701

    Article  PubMed  CAS  Google Scholar 

  53. Robertson SJ, Ennion SJ, Evans RJ, Edwards FA (2001) Synaptic P2X receptors. Curr Opin Neurobiol 11:378–386

    Article  PubMed  CAS  Google Scholar 

  54. Robitaille R (1995) Purinergic receptors and their activation by endogenous purines at perisynaptic glial cells of the frog neuromuscular junction. J Neurosci 15:7121–7131

    PubMed  CAS  Google Scholar 

  55. Silinsky EM, Gerzanich V, Vanner SM (1992) ATP mediates excitatory synaptic transmission in mammalian neurones. Br J Pharmacol 106:762–763

    PubMed  CAS  Google Scholar 

  56. 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

    Article  PubMed  CAS  Google Scholar 

  57. Strehler BL, Totter JR (1952) Firefly luminescence in the study of energy transfer mechanisms. I. Substrate and enzyme determination. Arch Biochem Biophys 40:28–41

    Article  PubMed  CAS  Google Scholar 

  58. Strehler BL, Totter JR (1954) Determination of ATP and related compounds: firefly luminescence and other methods. Methods Biochem Anal 1:341–356

    Article  PubMed  CAS  Google Scholar 

  59. Suadicani SO, Brosnan CF, Scemes E (2006) P2X7 receptors mediate ATP release and amplification of astrocytic intercellular Ca2+ signaling. J Neurosci 26:1378–1385

    Article  PubMed  CAS  Google Scholar 

  60. Surprenant A. (2004) P2X purinergic receptor. In: Encyclopedia of biological chemistry, vol 3. Elsevier, pp 183–187

  61. Surprenant A, Buell G, North RA (1995) P2X receptors bring new structure to ligand-gated ion channels. Trends Neurosci 18:224–229

    Article  PubMed  CAS  Google Scholar 

  62. Takano T, Kang J, Jaiswal JK, Simon SM, Lin JH, Yu Y, Li Y, Yang J, Dienel G, Zielke HR, Nedergaard M (2005) Receptor-mediated glutamate release from volume sensitive channels in astrocytes. Proc Natl Acad Sci U S A 102:16466–16471

    Article  PubMed  CAS  Google Scholar 

  63. Verkhratsky A, Steinhauser C (2000) Ion channels in glial cells. Brain Res Brain Res Rev 32:380–412

    Article  PubMed  CAS  Google Scholar 

  64. Verkhratsky A, Orkand RK, Kettenmann H (1998) Glial calcium: homeostasis and signaling function. Physiol Rev 78:99–141

    PubMed  CAS  Google Scholar 

  65. Vial C, Roberts JA, Evans RJ (2004) Molecular properties of ATP-gated P2X receptor ion channels. Trends Pharmacol Sci 25:487–493

    Article  PubMed  CAS  Google Scholar 

  66. Volterra A, Meldolesi J (2005) Astrocytes, from brain glue to communication elements: the revolution continues. Nat Rev Neurosci 6:626–640

    Article  PubMed  CAS  Google Scholar 

  67. Walz W, Gimpl G, Ohlemeyer C, Kettenmann H (1994) Extracellular ATP-induced currents in astrocytes: involvement of a cation channel. J Neurosci Res 38:12–18

    Article  PubMed  CAS  Google Scholar 

  68. White TD (1978) Release of ATP from a synaptosomal preparation by elevated extracellular K+ and by veratridine. J Neurochem 30:329–336

    Article  PubMed  CAS  Google Scholar 

  69. White TD (1984) Characteristics of neuronal release of ATP. Prog Neuropsychopharmacol Biol Psychiatry 8:487–493

    Article  PubMed  CAS  Google Scholar 

  70. White T, Potter P, Wonnacott S (1980) Depolarisation-induced release of ATP from cortical synaptosomes is not associated with acetylcholine release. J Neurochem 34:1109–1112

    Article  PubMed  CAS  Google Scholar 

  71. Zhang JM, Wang HK, Ye CQ, Ge W, Chen Y, Jiang ZL, Wu CP, Poo MM, Duan S (2003) ATP released by astrocytes mediates glutamatergic activity-dependent heterosynaptic suppression. Neuron 40:971–982

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Alexei Verkhratsky.

Rights and permissions

Reprints and permissions

About this article

Cite this article

North, R.A., Verkhratsky, A. Purinergic transmission in the central nervous system. Pflugers Arch - Eur J Physiol 452, 479–485 (2006). https://doi.org/10.1007/s00424-006-0060-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00424-006-0060-y

Keywords

Navigation