Cholinergic modulation of the release of 5-hydroxytryptamine from the guinea pig ileum.
Isolated segments 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 mumol/l). Scopolamine (0.1 mumol/l) did not affect the release of 5-HT and 5-HIAA, but antagonized the effect of oxotremorine. In the presence of TTX (1 mumol/l), oxotremorine (1 mumol/l) increased the release of 5-HT by 150% and that of 5-HIAA by 220%. This increase was completely blocked by scopolamine. Hexamethonium (100 mumol/l) and TTX (1 mumol/l) reduced the release of 5-HT by 32 and 40%, respectively. DMPP (10 mumol/l) 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 mumol/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.
D000818:Animals; D004759:Enterochromaffin Cells / Q000187:drug effects / Q000378:metabolism; D006168:Guinea Pigs; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology; D007082:Ileum / Q000378:metabolism; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D010095:Oxotremorine / Q000494:pharmacology; D011950:Receptors, Cholinergic / Q000502:physiology*; D011978:Receptors, Nicotinic / Q000502:physiology; D012601:Scopolamine / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism*
D006584:Hexamethonium Compounds; D011950:Receptors, Cholinergic; D011978:Receptors, Nicotinic; D012701:Serotonin; D018738:Hexamethonium; D010095:Oxotremorine; D012601:Scopolamine