title: Characterization of the muscarine receptors involved in the modulation of serotonin release from the vascularly perfused small intestine of guinea pig.
abstract: 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 mumol/l) which can discriminate between M1 and M2-receptor subtypes antagonized completely this inhibitory effect. In the presence of 1 mumol/l tetrodotoxin (TTx), all three muscarine receptor agonists increased the outflow of 5-HT and 5-HIAA. Oxotremorine (1 mumol/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 mumol/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.
authors: Department of Pharmacology, University of Mainz, Federal Republic of Germany.
authors: H
authors: H
authors: Schwörer
authors: K
authors: K
authors: Racké
authors: H
authors: H
authors: Kilbinger
mesh_terms: D008455:(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride / Q000494:pharmacology; D000818:Animals; D005260:Female; D006168:Guinea Pigs; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007421:Intestine, Small / Q000378:metabolism*; D008297:Male; D010095:Oxotremorine / Q000494:pharmacology; D010477:Perfusion; D010890:Pirenzepine / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D011976:Receptors, Muscarinic; D012701:Serotonin; D010890:Pirenzepine; D013779:Tetrodotoxin; D006897:Hydroxyindoleacetic Acid; D008455:(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride; D010095:Oxotremorine; D007213:Indomethacin