Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1988 May;94(1):228–234. doi: 10.1111/j.1476-5381.1988.tb11519.x

Prejunctional muscarinic (M1)-receptor interactions on guinea-pig ileum: lack of effect of cisapride.

J A Schuurkes 1, P J Van Bergen 1, J M Van Nueten 1
PMCID: PMC1853913  PMID: 2456809

Abstract

1. Cisapride stimulates gastrointestinal motility, probably by enhancing the release of acetylcholine from myenteric nerve endings. Such an effect could be mediated via presynaptic muscarinic (M1)-receptors. Our aim was to determine whether cisapride could antagonize the inhibitory effects of a M1-agonist, McN-A-343 or mimic the effects of a M1-antagonist, pirenzepine. 2. Longitudinal segments were suspended in Krebs solution (95% O2, 5% CO2, 37.5 degrees C) for isometric tension recording (preload 1 g) during electrical transmural stimulation (0.1 Hz, 1 ms, sub- or supramaximal current). 3. McN-A-343 (2.0 x 10(-6) M) reduced the contractile response to supramaximal stimulation (EC50 = 1.6 x 10(-6) M), but had no effect on the contractions induced by exogenous acetylcholine. 4. The inhibitory effect of McN-A-343 on the contractile response to electrical stimulation could be reversed by pirenzepine (EC50 = 1.6 x 10(-8) M) but not by atropine. At these concentrations pirenzepine itself did not modify the contractile response to electrical stimulation. However, at 50 times higher concentrations pirenzepine inhibited the response to electrical stimulation as well as the response to exogenous acetylcholine (EC50 = 8.5 x 10(-7) M). 5. Cisapride enhanced the contractile response to submaximal electrical stimulation by 49 +/- 10%. This stimulating effect of cisapride was not affected by the presence of pirenzepine but was reduced in the presence of McN-A-343 (22 +/- 7%). 6. In conclusion: the effects of McN-A-343 and pirenzepine on the electrically stimulated guinea-pig ileum are compatible with an interaction on presynaptic muscarinic-(M1)-receptors. Cisapride enhances the twitch amplitude via mechanisms independent of such M1-receptor interactions.

Full text

PDF
228

Selected References

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

  1. Brown D. A., Forward A., Marsh S. Antagonist discrimination between ganglionic and ileal muscarinic receptors. Br J Pharmacol. 1980;71(2):362–364. doi: 10.1111/j.1476-5381.1980.tb10948.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Buckley N. J., Burnstock G. Autoradiographic localization of peripheral M1 muscarinic receptors using [3H]pirenzepine. Brain Res. 1986 Jun 4;375(1):83–91. doi: 10.1016/0006-8993(86)90961-3. [DOI] [PubMed] [Google Scholar]
  3. Fosbraey P., Johnson E. S. Modulatory action on the twitch responses of the guinea-pig ileum of endogenous substances released by high frequency electrical stimulation. Eur J Pharmacol. 1980 Oct 31;67(4):393–402. doi: 10.1016/0014-2999(80)90180-6. [DOI] [PubMed] [Google Scholar]
  4. Fosbraey P., Johnson E. S. Release-modulating acetylcholine receptors in cholinergic neurones of the guinea-pig ileum. Br J Pharmacol. 1980 Feb;68(2):289–300. doi: 10.1111/j.1476-5381.1980.tb10418.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Fox J. E., Daniel E. E., Jury J., Robotham H. Muscarinic inhibition of canine small intestinal motility in vivo. Am J Physiol. 1985 May;248(5 Pt 1):G526–G531. doi: 10.1152/ajpgi.1985.248.5.G526. [DOI] [PubMed] [Google Scholar]
  6. Gilbert R., Rattan S., Goyal R. K. Pharmacologic identification, activation and antagonism of two muscarine receptor subtypes in the lower esophageal sphincter. J Pharmacol Exp Ther. 1984 Aug;230(2):284–291. [PubMed] [Google Scholar]
  7. Hammer R., Giachetti A. Muscarinic receptor subtypes: M1 and M2 biochemical and functional characterization. Life Sci. 1982 Dec 27;31(26):2991–2998. doi: 10.1016/0024-3205(82)90066-2. [DOI] [PubMed] [Google Scholar]
  8. Kilbinger H., Halim S., Lambrecht G., Weiler W., Wessler I. Comparison of affinities of muscarinic antagonists to pre- and postjunctional receptors in the guinea-pig ileum. Eur J Pharmacol. 1984 Aug 17;103(3-4):313–320. doi: 10.1016/0014-2999(84)90492-8. [DOI] [PubMed] [Google Scholar]
  9. Kilbinger H., Kruel R., Pfeuffer-Friederich I., Wessler I. The effects of metoclopramide on acetylcholine release and on smooth muscle response in the isolated guinea-pig ileum. Naunyn Schmiedebergs Arch Pharmacol. 1982 Jun;319(3):231–238. doi: 10.1007/BF00495871. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Lobbezoo M. W., Janszen F. H., Tulp M. T., Zwagemakers J. M. Differential effects of metoclopramide and zetidoline on gastrointestinal motility. Eur J Pharmacol. 1985 Jan 22;108(2):105–112. doi: 10.1016/0014-2999(85)90714-9. [DOI] [PubMed] [Google Scholar]
  12. North R. A., Slack B. E., Surprenant A. Muscarinic M1 and M2 receptors mediate depolarization and presynaptic inhibition in guinea-pig enteric nervous system. J Physiol. 1985 Nov;368:435–452. doi: 10.1113/jphysiol.1985.sp015867. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. PATON W. D. The action of morphine and related substances on contraction and on acetylcholine output of coaxially stimulated guinea-pig ileum. Br J Pharmacol Chemother. 1957 Mar;12(1):119–127. doi: 10.1111/j.1476-5381.1957.tb01373.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Schuurkes J. A., Van Nueten J. M., Van Daele P. G., Reyntjens A. J., Janssen P. A. Motor-stimulating properties of cisapride on isolated gastrointestinal preparations of the guinea pig. J Pharmacol Exp Ther. 1985 Sep;234(3):775–783. [PubMed] [Google Scholar]

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

RESOURCES