Skip to main content
PMC home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1996 Aug;118(8):2073–2078. doi: 10.1111/j.1476-5381.1996.tb15646.x

Differential effects of nitric oxide donors on basal and electrically evoked release of acetylcholine from guinea-pig myenteric neurones.

K Hebeiss 1, H Kilbinger 1
PMCID: PMC1909882  PMID: 8864545

Abstract

1. The effects of the nitric oxide (NO) donors, 3-morpholino-sydnonimine (SIN-1), S-nitroso-N-acetylpenicillamine (SNAP) and sodium nitroprusside on basal and electrically evoked release of [3H]-acetylcholine were studied in myenteric plexus longitudinal muscle preparations of the guinea-pig small intestine preincubated with [3H]-choline. 2. The NO donors concentration-dependently increased basal release of [3H]-acetylcholine. The increase in release was calcium-dependent and was prevented in the presence of tetrodotoxin. Superoxide dismutase (150 u ml-1) potentiated the effect of SIN-1. The selective inhibitor of soluble guanylyl cyclase, 1H-[1,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one (ODQ, 0.01-1 microM), antagonized the facilitatory effect of SNAP. 8-Bromo cyclic GMP and the cyclic GMP-specific phosphodiesterase inhibitor, zaprinast (both 0.1-1 mM), also enhanced basal [3H]-acetylcholine release. The effect of 10 microM SNAP was significantly enhanced in the presence of zaprinast. 3. The NO donors concentration-dependently inhibited the electrically evoked release of [3H]-acetylcholine, whereas 8-bromo cyclic GMP and zaprinast enhanced the evoked release. The inhibition of acetylcholine release by SNAP was not affected by ODQ (0.01-1 microM). 4. It is concluded that NO stimulates basal acetylcholine release from myenteric neurones through activation of guanylyl cyclase. In addition, NO inhibits the depolarization evoked release of acetylcholine by a presynaptic mechanism unrelated to cyclic GMP. The data imply that NO is not only an inhibitory transmitter to intestinal smooth muscles but also a modulator of cholinergic neurotransmission in the myenteric plexus.

Full text

PDF

Selected References

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

  1. Baccari M. C., Bertini M., Calamai F. Effects of L-NG-nitro arginine on cholinergic transmission in the gastric muscle of the rabbit. Neuroreport. 1993 Sep;4(9):1102–1104. [PubMed] [Google Scholar]
  2. Baccari M. C., Calamai F., Staderini G. Modulation of cholinergic transmission by nitric oxide, VIP and ATP in the gastric muscle. Neuroreport. 1994 Apr 14;5(8):905–908. doi: 10.1097/00001756-199404000-00013. [DOI] [PubMed] [Google Scholar]
  3. Barthó L., Lefebvre R. Nitric oxide induces acetylcholine-mediated contractions in the guinea-pig small intestine. Naunyn Schmiedebergs Arch Pharmacol. 1994 Nov;350(5):582–584. doi: 10.1007/BF00173030. [DOI] [PubMed] [Google Scholar]
  4. Beavo J. A., Reifsnyder D. H. Primary sequence of cyclic nucleotide phosphodiesterase isozymes and the design of selective inhibitors. Trends Pharmacol Sci. 1990 Apr;11(4):150–155. doi: 10.1016/0165-6147(90)90066-H. [DOI] [PubMed] [Google Scholar]
  5. Bredt D. S., Hwang P. M., Snyder S. H. Localization of nitric oxide synthase indicating a neural role for nitric oxide. Nature. 1990 Oct 25;347(6295):768–770. doi: 10.1038/347768a0. [DOI] [PubMed] [Google Scholar]
  6. Costa M., Furness J. B., Pompolo S., Brookes S. J., Bornstein J. C., Bredt D. S., Snyder S. H. Projections and chemical coding of neurons with immunoreactivity for nitric oxide synthase in the guinea-pig small intestine. Neurosci Lett. 1992 Dec 14;148(1-2):121–125. doi: 10.1016/0304-3940(92)90819-s. [DOI] [PubMed] [Google Scholar]
  7. Feelisch M., Ostrowski J., Noack E. On the mechanism of NO release from sydnonimines. J Cardiovasc Pharmacol. 1989;14 (Suppl 11):S13–S22. [PubMed] [Google Scholar]
  8. Fuder H., Muscholl E. Heteroreceptor-mediated modulation of noradrenaline and acetylcholine release from peripheral nerves. Rev Physiol Biochem Pharmacol. 1995;126:265–412. doi: 10.1007/BFb0049778. [DOI] [PubMed] [Google Scholar]
  9. Förstermann U., Closs E. I., Pollock J. S., Nakane M., Schwarz P., Gath I., Kleinert H. Nitric oxide synthase isozymes. Characterization, purification, molecular cloning, and functions. Hypertension. 1994 Jun;23(6 Pt 2):1121–1131. doi: 10.1161/01.hyp.23.6.1121. [DOI] [PubMed] [Google Scholar]
  10. Garthwaite J., Southam E., Boulton C. L., Nielsen E. B., Schmidt K., Mayer B. Potent and selective inhibition of nitric oxide-sensitive guanylyl cyclase by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one. Mol Pharmacol. 1995 Aug;48(2):184–188. [PubMed] [Google Scholar]
  11. Guevara-Guzman R., Emson P. C., Kendrick K. M. Modulation of in vivo striatal transmitter release by nitric oxide and cyclic GMP. J Neurochem. 1994 Feb;62(2):807–810. doi: 10.1046/j.1471-4159.1994.62020807.x. [DOI] [PubMed] [Google Scholar]
  12. Hryhorenko L. M., Woskowska Z., Fox-Threlkeld J. A. Nitric oxide (NO) inhibits release of acetylcholine from nerves of isolated circular muscle of the canine ileum: relationship to motility and release of nitric oxide. J Pharmacol Exp Ther. 1994 Nov;271(2):918–926. [PubMed] [Google Scholar]
  13. Kilbinger H., Nafziger M. Two types of neuronal muscarine receptors modulating acetylcholine release from guinea-pig myenteric plexus. Naunyn Schmiedebergs Arch Pharmacol. 1985 Jan;328(3):304–309. doi: 10.1007/BF00515558. [DOI] [PubMed] [Google Scholar]
  14. Kilbinger H., Wolf D. Increase by NO synthase inhibitors of acetylcholine release from guinea-pig myenteric plexus. Naunyn Schmiedebergs Arch Pharmacol. 1994 May;349(5):543–545. doi: 10.1007/BF00169145. [DOI] [PubMed] [Google Scholar]
  15. Knudsen M. A., Tøttrup A. A possible role of the L-arginine-nitric oxide pathway in the modulation of cholinergic transmission in the guinea-pig taenia coli. Br J Pharmacol. 1992 Nov;107(3):837–841. doi: 10.1111/j.1476-5381.1992.tb14533.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lefebvre R. A., De Vriese A., Smits G. J. Influence of vasoactive intestinal polypeptide and NG-nitro-L-arginine methyl ester on cholinergic neurotransmission in the rat gastric fundus. Eur J Pharmacol. 1992 Oct 20;221(2-3):235–242. doi: 10.1016/0014-2999(92)90707-b. [DOI] [PubMed] [Google Scholar]
  17. Lefebvre R. A. Nitric oxide in the peripheral nervous system. Ann Med. 1995 Jun;27(3):379–388. doi: 10.3109/07853899509002591. [DOI] [PubMed] [Google Scholar]
  18. Llewellyn-Smith I. J., Song Z. M., Costa M., Bredt D. S., Snyder S. H. Ultrastructural localization of nitric oxide synthase immunoreactivity in guinea-pig enteric neurons. Brain Res. 1992 Apr 17;577(2):337–342. doi: 10.1016/0006-8993(92)90294-j. [DOI] [PubMed] [Google Scholar]
  19. Lonart G., Wang J., Johnson K. M. Nitric oxide induces neurotransmitter release from hippocampal slices. Eur J Pharmacol. 1992 Sep 22;220(2-3):271–272. doi: 10.1016/0014-2999(92)90759-w. [DOI] [PubMed] [Google Scholar]
  20. Marczin N., Ryan U. S., Catravas J. D. Methylene blue inhibits nitrovasodilator- and endothelium-derived relaxing factor-induced cyclic GMP accumulation in cultured pulmonary arterial smooth muscle cells via generation of superoxide anion. J Pharmacol Exp Ther. 1992 Oct;263(1):170–179. [PubMed] [Google Scholar]
  21. Matusak O., Kuchel O., Hamet P. Effect of atrial natriuretic factor and 8-bromo cyclic guanosine 3':5'-monophosphate on [3H]acetylcholine outflow from myenteric-plexus longitudinal muscle of the guinea pig. J Pharmacol Exp Ther. 1991 Apr;257(1):107–113. [PubMed] [Google Scholar]
  22. Mayer B., Brunner F., Schmidt K. Inhibition of nitric oxide synthesis by methylene blue. Biochem Pharmacol. 1993 Jan 26;45(2):367–374. doi: 10.1016/0006-2952(93)90072-5. [DOI] [PubMed] [Google Scholar]
  23. Meulemans A., Mothet J. P., Schirar A., Fossier P., Tauc L., Baux G. A nitric oxide synthase activity is involved in the modulation of acetylcholine release in Aplysia ganglion neurons: a histological, voltammetric and electrophysiological study. Neuroscience. 1995 Dec;69(3):985–995. doi: 10.1016/0306-4522(95)00316-b. [DOI] [PubMed] [Google Scholar]
  24. Ohkuma S., Katsura M., Guo J. L., Hasegawa T., Kuriyama K. Participation of peroxynitrite in acetylcholine release induced by nitric oxide generators. Neurosci Lett. 1995 Jan 9;183(3):151–154. doi: 10.1016/0304-3940(94)11137-8. [DOI] [PubMed] [Google Scholar]
  25. Osthaus L. E., Galligan J. J. Antagonists of nitric oxide synthesis inhibit nerve-mediated relaxations of longitudinal muscle in guinea pig ileum. J Pharmacol Exp Ther. 1992 Jan;260(1):140–145. [PubMed] [Google Scholar]
  26. Prast H., Fischer H., Werner E., Werner-Felmayer G., Philippu A. Nitric oxide modulates the release of acetylcholine in the ventral striatum of the freely moving rat. Naunyn Schmiedebergs Arch Pharmacol. 1995 Jul;352(1):67–73. doi: 10.1007/BF00169191. [DOI] [PubMed] [Google Scholar]
  27. Prast H., Philippu A. Nitric oxide releases acetylcholine in the basal forebrain. Eur J Pharmacol. 1992 May 27;216(1):139–140. doi: 10.1016/0014-2999(92)90223-q. [DOI] [PubMed] [Google Scholar]
  28. Sanders K. M., Ward S. M. Nitric oxide as a mediator of nonadrenergic noncholinergic neurotransmission. Am J Physiol. 1992 Mar;262(3 Pt 1):G379–G392. doi: 10.1152/ajpgi.1992.262.3.G379. [DOI] [PubMed] [Google Scholar]
  29. Shuttleworth C. W., Xue C., Ward S. M., de Vente J., Sanders K. M. Immunohistochemical localization of 3',5'-cyclic guanosine monophosphate in the canine proximal colon: responses to nitric oxide and electrical stimulation of enteric inhibitory neurons. Neuroscience. 1993 Sep;56(2):513–522. doi: 10.1016/0306-4522(93)90350-o. [DOI] [PubMed] [Google Scholar]
  30. Sun P., Kanthasamy A., Yim G. K., Isom G. E. Inhibition of potassium-stimulated dopamine release by the nitric oxide generator isosorbide dinitrate. Neuropharmacology. 1995 Feb;34(2):205–210. doi: 10.1016/0028-3908(94)00151-h. [DOI] [PubMed] [Google Scholar]
  31. Tamura K., Schemann M., Wood J. D. Actions of nitric oxide-generating sodium nitroprusside in myenteric plexus of guinea pig small intestine. Am J Physiol. 1993 Nov;265(5 Pt 1):G887–G893. doi: 10.1152/ajpgi.1993.265.5.G887. [DOI] [PubMed] [Google Scholar]
  32. Wiklund C. U., Olgart C., Wiklund N. P., Gustafsson L. E. Modulation of cholinergic and substance P-like neurotransmission by nitric oxide in the guinea-pig ileum. Br J Pharmacol. 1993 Oct;110(2):833–839. doi: 10.1111/j.1476-5381.1993.tb13888.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Wiklund C. U., Wiklund N. P., Gustafsson L. E. Modulation of neuroeffector transmission by endogenous nitric oxide: a role for acetylcholine receptor-activated nitric oxide formation, as indicated by measurements of nitric oxide/nitrite release. Eur J Pharmacol. 1993 Aug 24;240(2-3):235–242. doi: 10.1016/0014-2999(93)90904-v. [DOI] [PubMed] [Google Scholar]
  34. Wiklund N. P., Leone A. M., Gustafsson L. E., Moncada S. Release of nitric oxide evoked by nerve stimulation in guinea-pig intestine. Neuroscience. 1993 Apr;53(3):607–611. doi: 10.1016/0306-4522(93)90609-j. [DOI] [PubMed] [Google Scholar]

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

RESOURCES