Summary
Isolated segements of the guinea pig ileum were vascularly perfused and the release of 5-HT and its metabolite 5-HIAA into the portal venous effluent determined by HPLC with electrochemical detection. Test substances were applied via the arterial perfusion medium. Oxotremorine inhibited concentration-dependently the release of 5-HT and 5-HIAA (by 47% at 1 μmol/l). Scopolamine (0.1 μmol/1) did not affect the release of 5-HT and 5-HIAA, but antagonized the effect of oxotremorine. In the presence of TTX (1 μmol/1) oxotremorine (1 pmol/1) increased the release of 5-HT by 150% and that of 5-HIAA by 220%. This increase was completely blocked by scopolamine. Hexamethonium (100 pmol/1) and TTX (1 pmol/1) reduced the release of 5-HT by 32 and 40%, respectively. DMPP (10 pmol/1) increased the release of 5-HT by 57%, and this effect was prevented by hexamethonium. Neither DMPP nor hexamethonium significantly affected the release of 5-HIAA. The enhancing effect of DMPP on 5-HT release was increased and prolonged in the presence of TTX or scopolamine. Nicotine (1, 10 or 30 μmol/l) alone did not cause a consistent increase in the release of 5-HT. However, in the presence of scopolamine nicotine increased the release of 5-HT by 57%. In conclusion, the release of intestinal 5-HT is facilitated via muscarine and nicotine receptors located on the enterochromaffin cells. Indirect evidence suggests that the release of 5-HT is additionally modulated by an as yet unknown inhibitory neurotransmitter released by muscarine receptor activation.
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Abbreviations
- DMPP:
-
1,1-dimethyl-4-phenylpiperazinium
- 5-HT:
-
5-hydroxytryptamine
- 5-HIAA:
-
5-hydroxyindoleacetic acid
- TTX:
-
tetrodotoxin
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Schwörer, H., Racké, K. & Kilbinger, H. Cholinergic modulation of the release of 5-hydroxytryptamine from the guinea pig ileum. Naunyn-Schmiedeberg's Arch Pharmacol 336, 127–132 (1987). https://doi.org/10.1007/BF00165795
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DOI: https://doi.org/10.1007/BF00165795