Skip to main content
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1996 Jul;118(5):1232–1236. doi: 10.1111/j.1476-5381.1996.tb15528.x

Action of suramin upon ecto-apyrase activity and synaptic depression of Torpedo electric organ.

E Martí 1, C Cantí 1, I Gómez de Aranda 1, F Miralles 1, C Solsona 1
PMCID: PMC1909591  PMID: 8818348

Abstract

1. The role of ATP, which is co-released with acetylcholine in synaptic contacts of Torpedo electric organ, was investigated by use of suramin. Suramin [8-(3-benzamido-4-methylbenzamido)naphthalene-1,3,5-trisulphoni c acid], a P2 purinoceptor antagonist, potently inhibited in a non-competitive manner the ecto-apyrase activity associated with plasma membrane isolated from cholinergic nerve terminals of Torpedo electric organ. The Ki was 30 microM and 43 microM for Ca(2+)-ADPase and Ca(2+)-ATPase respectively. 2. In Torpedo electric organ, repetitive stimulation decreased the evoked synaptic current by 51%. However, when fragments of electric organ were incubated with suramin the evoked synaptic current declined by only 14%. Fragments incubated with the selective A1 purinoceptor antagonist, DPCPX, showed 5% synaptic depression. 3. The effects of suramin and DPCPX on synaptic depression were not addictive. Synaptic depression may thus be linked to endogenous adenosine formed by dephosphorylation of released ATP by an ecto-apyrase. The final effector in synaptic depression, adenosine, acts via the A1 purinoceptor. 4. ATP hydrolysis is prevented in the presence of suramin. It slightly increased (20%) the mean amplitude of spontaneous miniature endplate currents. The frequency distribution of the amplitude of spontaneous events was shifted to the right, indicating that ATP, when not degraded, may modulate the activation of nicotinic acetylcholine receptors activated by the quantal secretion of acetycholine.

Full text

PDF
1232

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bailey S. J., Hourani S. M. Differential effects of suramin on P2-purinoceptors mediating contraction of the guinea-pig vas deferens and urinary bladder. Br J Pharmacol. 1994 May;112(1):219–225. doi: 10.1111/j.1476-5381.1994.tb13055.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bailey S. J., Hourani S. M. Effects of suramin on contractions of the guinea-pig vas deferens induced by analogues of adenosine 5'-triphosphate. Br J Pharmacol. 1995 Mar;114(6):1125–1132. doi: 10.1111/j.1476-5381.1995.tb13324.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Barajas-López C., Barrientos M., Espinosa-Luna R. Suramin increases the efficacy of ATP to activate an inward current in myenteric neurons from guinea-pig ileum. Eur J Pharmacol. 1993 Nov 30;250(1):141–145. doi: 10.1016/0014-2999(93)90631-q. [DOI] [PubMed] [Google Scholar]
  4. Battastini A. M., da Rocha J. B., Barcellos C. K., Dias R. D., Sarkis J. J. Characterization of an ATP diphosphohydrolase (EC 3.6.1.5) in synaptosomes from cerebral cortex of adult rats. Neurochem Res. 1991 Dec;16(12):1303–1310. doi: 10.1007/BF00966661. [DOI] [PubMed] [Google Scholar]
  5. Bean B. P. Pharmacology and electrophysiology of ATP-activated ion channels. Trends Pharmacol Sci. 1992 Mar;13(3):87–90. doi: 10.1016/0165-6147(92)90032-2. [DOI] [PubMed] [Google Scholar]
  6. Beukers M. W., Kerkhof C. J., van Rhee M. A., Ardanuy U., Gurgel C., Widjaja H., Nickel P., IJzerman A. P., Soudijn W. Suramin analogs, divalent cations and ATP gamma S as inhibitors of ecto-ATPase. Naunyn Schmiedebergs Arch Pharmacol. 1995 May;351(5):523–528. doi: 10.1007/BF00171044. [DOI] [PubMed] [Google Scholar]
  7. Cantí C., Martí E., Marsal J., Solsona C. Tacrine-induced increase in the release of spontaneous high quantal content events in Torpedo electric organ. Br J Pharmacol. 1994 May;112(1):19–22. doi: 10.1111/j.1476-5381.1994.tb13022.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Carlson B. J., Raftery M. A. Specific binding of ATP to extracellular sites on Torpedo acetylcholine receptor. Biochemistry. 1993 Jul 27;32(29):7329–7333. doi: 10.1021/bi00080a002. [DOI] [PubMed] [Google Scholar]
  9. Chen C. C., Akopian A. N., Sivilotti L., Colquhoun D., Burnstock G., Wood J. N. A P2X purinoceptor expressed by a subset of sensory neurons. Nature. 1995 Oct 5;377(6548):428–431. doi: 10.1038/377428a0. [DOI] [PubMed] [Google Scholar]
  10. Dowdall M. J., Boyne A. F., Whittaker V. P. Adenosine triphosphate. A constituent of cholinergic synaptic vesicles. Biochem J. 1974 Apr;140(1):1–12. doi: 10.1042/bj1400001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Dunant Y., Esquerda J. E., Loctin F., Marsal J., Muller D. Botulinum toxin inhibits quantal acetylcholine release and energy metabolism in the Torpedo electric organ. J Physiol. 1987 Apr;385:677–692. doi: 10.1113/jphysiol.1987.sp016514. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Eterović V. A., Li L., Palma A., McNamee M. G. Regulation of nicotinic acetylcholine receptor function by adenine nucleotides. Cell Mol Neurobiol. 1990 Sep;10(3):423–433. doi: 10.1007/BF00711184. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Evans R. J., Derkach V., Surprenant A. ATP mediates fast synaptic transmission in mammalian neurons. Nature. 1992 Jun 11;357(6378):503–505. doi: 10.1038/357503a0. [DOI] [PubMed] [Google Scholar]
  14. Fu W. M. Potentiation by ATP of the postsynaptic acetylcholine response at developing neuromuscular synapses in Xenopus cell cultures. J Physiol. 1994 Jun 15;477(Pt 3):449–458. doi: 10.1113/jphysiol.1994.sp020206. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Grondal E. J., Zimmermann H. Ectonucleotidase activities associated with cholinergic synaptosomes isolated from Torpedo electric organ. J Neurochem. 1986 Sep;47(3):871–881. doi: 10.1111/j.1471-4159.1986.tb00692.x. [DOI] [PubMed] [Google Scholar]
  16. Grondal E. J., Zimmermann H. Purification, characterization and cellular localization of 5'-nucleotidase from Torpedo electric organ. Biochem J. 1987 Aug 1;245(3):805–810. doi: 10.1042/bj2450805. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Haleen S. J., Steffen R. P., Hamilton H. W. PD 116,948, a highly selective A1 adenosine receptor antagonist. Life Sci. 1987 Feb 9;40(6):555–561. doi: 10.1016/0024-3205(87)90369-9. [DOI] [PubMed] [Google Scholar]
  18. Henning R. H., Nelemans A., Houwertjes M., Agoston S. Reversal by suramin of neuromuscular block produced by pancuronium in the anaesthetized rat. Br J Pharmacol. 1993 Mar;108(3):717–720. doi: 10.1111/j.1476-5381.1993.tb12867.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Henning R. H., Nelemans A., Scaf A. H., Van Eekeren J., Agoston S., Den Hertog A. Suramin reverses non-depolarizing neuromuscular blockade in rat diaphragm. Eur J Pharmacol. 1992 May 27;216(1):73–79. doi: 10.1016/0014-2999(92)90211-l. [DOI] [PubMed] [Google Scholar]
  20. Hourani S. M., Chown J. A. The effects of some possible inhibitors of ectonucleotidases on the breakdown and pharmacological effects of ATP in the guinea-pig urinary bladder. Gen Pharmacol. 1989;20(4):413–416. doi: 10.1016/0306-3623(89)90188-2. [DOI] [PubMed] [Google Scholar]
  21. Hoyle C. H. Pharmacological activity of adenine dinucleotides in the periphery: possible receptor classes and transmitter function. Gen Pharmacol. 1990;21(6):827–831. doi: 10.1016/0306-3623(90)90440-w. [DOI] [PubMed] [Google Scholar]
  22. Igusa Y. Adenosine 5'-triphosphate activates acetylcholine receptor channels in cultured Xenopus myotomal muscle cells. J Physiol. 1988 Nov;405:169–185. doi: 10.1113/jphysiol.1988.sp017327. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Israël M., Lesbats B., Manaranche R., Meunier F. M., Frachon P. Retrograde inhibition of transmitter release by ATP. J Neurochem. 1980 Apr;34(4):923–932. doi: 10.1111/j.1471-4159.1980.tb09667.x. [DOI] [PubMed] [Google Scholar]
  24. Israël M., Lesbats B., Meunier F. M., Stinnakre J. Postsynaptic release of adenosine triphosphate induced by single impulse transmitter action. Proc R Soc Lond B Biol Sci. 1976 Jun 30;193(1113):461–468. doi: 10.1098/rspb.1976.0058. [DOI] [PubMed] [Google Scholar]
  25. Knowles A. F., Isler R. E., Reece J. F. The common occurrence of ATP diphosphohydrolase in mammalian plasma membranes. Biochim Biophys Acta. 1983 May 26;731(1):88–96. doi: 10.1016/0005-2736(83)90401-7. [DOI] [PubMed] [Google Scholar]
  26. Lanzetta P. A., Alvarez L. J., Reinach P. S., Candia O. A. An improved assay for nanomole amounts of inorganic phosphate. Anal Biochem. 1979 Nov 15;100(1):95–97. doi: 10.1016/0003-2697(79)90115-5. [DOI] [PubMed] [Google Scholar]
  27. LeBel D., Poirier G. G., Phaneuf S., St-Jean P., Laliberté J. F., Beaudoin A. R. Characterization and purification of a calcium-sensitive ATP diphosphohydrolase from pig pancreas. J Biol Chem. 1980 Feb 10;255(3):1227–1233. [PubMed] [Google Scholar]
  28. Lewis C., Neidhart S., Holy C., North R. A., Buell G., Surprenant A. Coexpression of P2X2 and P2X3 receptor subunits can account for ATP-gated currents in sensory neurons. Nature. 1995 Oct 5;377(6548):432–435. doi: 10.1038/377432a0. [DOI] [PubMed] [Google Scholar]
  29. Meghji P., Burnstock G. Inhibition of extracellular ATP degradation in endothelial cells. Life Sci. 1995;57(8):763–771. doi: 10.1016/0024-3205(95)02004-3. [DOI] [PubMed] [Google Scholar]
  30. Meunier F., Israël M., Lesbats B. Release of ATP from stimulated nerve electroplaque junctions. Nature. 1975 Oct 2;257(5525):407–408. doi: 10.1038/257407a0. [DOI] [PubMed] [Google Scholar]
  31. Morel N., Marsal J., Manaranche R., Lazereg S., Mazie J. C., Israel M. Large-scale purification of presynaptic plasma membranes from Torpedo marmorata electric organ. J Cell Biol. 1985 Nov;101(5 Pt 1):1757–1762. doi: 10.1083/jcb.101.5.1757. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Morel N., Meunier F. M. Simultaneous release of acetylcholine and ATP from stimulated cholinergic synaptosomes. J Neurochem. 1981 May;36(5):1766–1773. doi: 10.1111/j.1471-4159.1981.tb00429.x. [DOI] [PubMed] [Google Scholar]
  33. Muller D., Dunant Y. Spontaneous quantal and subquantal transmitter release at the Torpedo nerve-electroplaque junction. Neuroscience. 1987 Mar;20(3):911–921. doi: 10.1016/0306-4522(87)90252-1. [DOI] [PubMed] [Google Scholar]
  34. Muller D., Loctin F., Dunant Y. Inhibition of evoked acetylcholine release: two different mechanisms in the Torpedo electric organ. Eur J Pharmacol. 1987 Jan 13;133(2):225–234. doi: 10.1016/0014-2999(87)90154-3. [DOI] [PubMed] [Google Scholar]
  35. Nakazawa K. ATP-activated current and its interaction with acetylcholine-activated current in rat sympathetic neurons. J Neurosci. 1994 Feb;14(2):740–750. doi: 10.1523/JNEUROSCI.14-02-00740.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Redman R. S., Silinsky E. M. ATP released together with acetylcholine as the mediator of neuromuscular depression at frog motor nerve endings. J Physiol. 1994 May 15;477(Pt 1):117–127. doi: 10.1113/jphysiol.1994.sp020176. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Richardson P. J., Brown S. J., Bailyes E. M., Luzio J. P. Ectoenzymes control adenosine modulation of immunoisolated cholinergic synapses. Nature. 1987 May 21;327(6119):232–234. doi: 10.1038/327232a0. [DOI] [PubMed] [Google Scholar]
  38. Sarkis J. J., Salto C. Characterization of a synaptosomal ATP diphosphohydrolase from the electric organ of Torpedo marmorata. Brain Res Bull. 1991 Jun;26(6):871–876. doi: 10.1016/0361-9230(91)90251-e. [DOI] [PubMed] [Google Scholar]
  39. Silinsky E. M. On the association between transmitter secretion and the release of adenine nucleotides from mammalian motor nerve terminals. J Physiol. 1975 May;247(1):145–162. doi: 10.1113/jphysiol.1975.sp010925. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Solsona C., Marsal J., Saltó C. The release of adenosine at the electric organ of Torpedo. A study using a continuous chemiluminescent method. Neurochem Res. 1990 Jan;15(1):77–82. doi: 10.1007/BF00969187. [DOI] [PubMed] [Google Scholar]
  41. Voogd T. E., Vansterkenburg E. L., Wilting J., Janssen L. H. Recent research on the biological activity of suramin. Pharmacol Rev. 1993 Jun;45(2):177–203. [PubMed] [Google Scholar]
  42. Wieraszko A. Facilitation of hippocampal potentials by suramin. J Neurochem. 1995 Mar;64(3):1097–1101. doi: 10.1046/j.1471-4159.1995.64031097.x. [DOI] [PubMed] [Google Scholar]
  43. Ziganshin A. U., Ziganshina L. E., King B. E., Burnstock G. Characteristics of ecto-ATPase of Xenopus oocytes and the inhibitory actions of suramin on ATP breakdown. Pflugers Arch. 1995 Jan;429(3):412–418. doi: 10.1007/BF00374157. [DOI] [PubMed] [Google Scholar]
  44. Zimmermann H. Signalling via ATP in the nervous system. Trends Neurosci. 1994 Oct;17(10):420–426. doi: 10.1016/0166-2236(94)90016-7. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES