Summary
Isolated small intestinal segments of the guinea pig were arterially perfused and the release of 5-hydroxytryptamine (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) into the portal venous effluent measured by HPLC with electrochemical detection. Test substances were applied via the arterial perfusion medium. McN-A-343, pilocarpine and oxotremorine inhibited concentration-dependently the outflow of 5-HT and 5-HIAA. Pirenzepine (0.03–0.1 μmol/l) which can discriminate between M1 and M2-receptor subtypes antagonized completely this inhibitory effect. In the presence of 1 μmol/l tetrodotoxin (TTx), all three muscarine receptor agonists increased the outflow of 5-HT and 5-HIAA. Oxotremorine 1 μmol/l was most effective and increased the outflow of 5-HT by 145%, that of 5-HIAA by 235%. McN-A-343 and pilocarpine, both at a concentration of 10 μmol/l, increased the outflow of 5-HT by about 40%, that of 5-HIAA by 50% and 71%, respectively. The stimulatory effect of oxotremorine was competitively antagonized by pirenzepine; a pA2 value of 7.70 was calculated. In conclusion, the cholinergic modulation of the release of 5-HT from the enterochromaffin cells consists of an indirect inhibitory (via the release of a neurotransmitter) and a direct stimulatory component. Muscarine receptors mediating the indirect effect may belong to the M1-subtype whereas the direct stimulatory effect may be mediated by a mixed population of M1 and M2 receptors or by a subtype of M1 receptors.
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Schwörer, H., Racké, K. & Kilbinger, H. Characterization of the muscarine receptors involved in the modulation of serotonin release from the vascularly perfused small intestine of guinea pig. Naunyn-Schmiedeberg's Arch Pharmacol 339, 263–267 (1989). https://doi.org/10.1007/BF00173575
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DOI: https://doi.org/10.1007/BF00173575