Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 331, Issue 4, pp 311–315 | Cite as

The effects of LSD in the guinea-pig ileum

Inhibition of acetylcholine release and stimulation of smooth muscle
  • I. Pfeuffer-Friederich
  • H. Kilbinger
Article
Received:
Accepted:

Summary

  1. 1.

    The effects of lysergic acid diethylamide (LSD) on acetylcholine release and on smooth muscle tone were studied in the myenteric plexus-longitudinal muscle preparation of the guinea pig.

     
  2. 2.

    LSD (0.01–10 μM) depressed in a concentration-dependent manner the electrically-evoked [3H]-acetylcholine outflow from strips preincubated with [3H]-choline. The maximal effect was a 45% inhibition by 1 μM LSD. The spontaneous outflow was not affected. Metitepine competitively antagonized (pA2 8.0) the LSD-induced reduction of the evoked outflow. Tolazoline and mepyramine did not affect the inhibitory action of LSD.

     
  3. 3.

    The contractions in response to electrical stimulation were enhanced by 34% in the presence of 0.1 μM LSD. Other concentrations of LSD did not affect the twitches.

     
  4. 4.

    LSD caused an increase in muscle tone which was antagonized non-competitively by mepyramine, metitepine and ketanserin. Ketanserin was a competitive antagonist against the histamine-induced contractions of the longitudinal muscle (pA2 8.49).

     
  5. 5.

    The results suggest that LSD stimulates presynaptically located 5-HT receptors and thereby decreases the evoked acetylcholine release. In addition, LSD increases smooth muscle tone either directly through stimulation of H1 receptors or indirectly via histamine release.

     

Key words

Guinea-pig ilcum LSD 5-HT receptors Histamine receptors 
This is a preview of subscription content, log in to check access.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Ambache N, Killick SW, Srinivasan V, Aboo Zar M (1975) Effects of lysergic acid diethylamide on autonomic post-ganglionic transmission. J Physiol 246:571–593Google Scholar
  2. Arunlakshana O, Schild HO (1959) Some quantitative uses of drug antagonists. Br J Pharmacol 14:48–58Google Scholar
  3. Dale MM, Zilletti L (1970) The Schultz-Dale response of the longitudinal muscle strip preparation of guinea-pig ileum. Br J Pharmacol 39:542–555Google Scholar
  4. Drew GM (1978) Pharmacological characterization of the presynaptic adrenoceptors regulating cholinergic activity in the guinea-pig ileum. Br J Pharmacol 64:293–300Google Scholar
  5. Dunnett CW (1964) New tables for multiple comparisons with a control. Biometrics 20:482–491Google Scholar
  6. Gaddum JH, Picarelli ZP (1957) Two kinds of tryptamine receptors. Br J Pharmacol 12:323–328Google Scholar
  7. Görich R, Weihrauch TR, Kilbinger H (1982) The inhibition by dopamine of cholinergic transmission in the isolated guinea-pig ileum: mediation through α-adrenoceptors. Naunyn-Schmiedeberg's Arch Pharmacol 308–312Google Scholar
  8. Kilbinger H, Nafziger M (1985) Two types of neuronal muscarine receptors modulating acetylcholine release from guinea-pig myenteric plexus. Naunyn-Schmiedeberg's Arch Pharmacol 328:304–309Google Scholar
  9. Kilbinger H, Pfeuffer-Friederich I (1985) Two types of receptors for 5-hydroxytryptamine on the cholinergic nerves of the guinea-pig myenteric plexus. Br J Pharmacol 85:529–539Google Scholar
  10. Langer SZ, Moret C (1982) Citalopram antagonizes the stimulation by lysergic acid diethylamide of presynaptic inhibitory serotonin autoreceptors in the rat hypothalamus. J Pharmacol Exp Ther 222:220–226Google Scholar
  11. Leysen JE, Awouters F, Kennis L, Laduron PM, Vandenberk J, Janssen PAJ (1981) Receptor binding profile of R 41 468, a novel antagonist at 5-HT2 receptors. Life Sci 28:1115–1122Google Scholar
  12. McGrath JC (1979) Modification of release by lysergic acid diethylamide. In: Paton DM (ed) The release of catecholamines from adrenergic neurons. Pergamon Press, Oxford, pp 229–239Google Scholar
  13. Müller-Schweinitzer E, Weidmann H (1978) Basic pharmacological properties. In: Berde B, Schild HO (eds) Handb Exp Pharmacol, vol 49, Ergot alkaloids and related compounds. Springer, Berlin Heidelberg New York, pp 87–232Google Scholar
  14. North RA, Henderson G, Katayama Y, Johnson SM (1980) Electrophysiological evidence for presynaptic inhibition of acetylcholine relase by 5-hydroxytryptamine in the enteric nervous system. Neuroscience 5:581–586Google Scholar
  15. Pettibone DJ, Pflueger AB (1984) Effects of methiothepin and lysergic acid diethylamide on serotonin release in vitro and serotonin synthesis in vivo: possible relation to serotonin autoreceptor function. J Neurochem 43:83–90Google Scholar
  16. Pfeuffer-Friederich I, Apel H (1985) Differences between serotonin (5-HT) receptors on the smooth muscle of the rat stomach and the guinea-pig ileum. Naunyn-Schmiedeberg's Arch Pharmacol 329:R83Google Scholar
  17. Pfeuffer-Friederich I, Kilbinger H (1983) LSD induced inhibition of evoked acetylcholine release from guinea-pig myenteric plexus is mediated through serotonin (5-HT) receptors. Naunyn-Schmiedeberg's Arch Pharmacol 324:R40Google Scholar
  18. Van Rossum (1963) Cumulative dose-response curves. II. Technique for the making of dose-response curves in isolated organs and the evaluation of drug parameters. Arch Int Pharmacodyn 141:299–330Google Scholar

Copyright information

© Springer-Verlag 1985

Authors and Affiliations

  • I. Pfeuffer-Friederich
    • 1
  • H. Kilbinger
    • 1
  1. 1.Pharmakologisches Institut der Universität MainzMainzFederal Republic of Germany

Personalised recommendations