Two types of receptors for 5-hydroxytryptamine on the cholinergic nerves of the guinea-pig myenteric plexus.
The effects of 5-hydroxytryptamine (5-HT) on spontaneous and electrically-evoked release of [3H]-acetylcholine (ACh) from guinea-pig myenteric plexus preparations preincubated with [3H]-choline have been investigated in the absence of cholinesterase inhibitors. 5-HT caused a transient increase in spontaneous release and an inhibition of the electrically-evoked release of [3H]-ACh. The 5-HT-induced contractions of the longitudinal muscle were clearly related to the increase in spontaneous release. The inhibitory effect was not due to activation of alpha-adrenoceptors since it was also observed in the presence of tolazoline and on strips from reserpine-pretreated guinea-pigs. After desensitization of the excitatory 5-HT receptors with 5-HT or metoclopramide the effects of 5-HT on spontaneous [3H]-ACh release were largely reduced. A variety of established antagonists at neuronal 5-HT receptors (i.e. metitepine 0.1-1 microM; methysergide 1 microM; ketanserin 0.1-1 microM; MDL 72222 0.1 microM; tropacocaine 1 microM) failed to block the excitation. The inhibition by 5-HT of the electrically evoked [3H]-ACh release was competitively antagonized by metitepine (pA2 7.6) and methysergide (pA2 7.0) but not by ketanserin. Tachyphylaxis to the inhibitory action of 5-HT did not occur. The results suggest that the excitatory 5-HT receptor ('M'-receptor) differs in its pharmacological properties from other neuronal 5-HT receptors. The presynaptically located inhibitory receptor may roughly correspond to the 5-HT1 receptor subtype but probably differs from the 5-HT autoreceptor.
Kilbinger
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H
Pfeuffer-Friederich
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I
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001667:Binding, Competitive; D003042:Cocaine / Q000031:analogs & derivatives / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D007650:Ketanserin; D008297:Male; D008719:Methiothepin / Q000494:pharmacology; D008784:Methysergide / Q000494:pharmacology; D008787:Metoclopramide / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009197:Myenteric Plexus / Q000187:drug effects / Q000378:metabolism*; D010880:Piperidines / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000378:metabolism*; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D014326:Tropanes / Q000494:pharmacology
D010880:Piperidines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D014326:Tropanes; C005862:tropacocaine; D012701:Serotonin; D008719:Methiothepin; D007650:Ketanserin; D003042:Cocaine; D008787:Metoclopramide; D000109:Acetylcholine; C042253:bemesetron; D008784:Methysergide