Analysis of ergotamine - 5-HT interaction on the isolated rat stomach preparation.
The effect of ergotamine on the isolated rat stomach and its influence on the response to ACh and 5-HT were investigated. The log dose-response curve of ergotamine was bell-shaped. Extension of the incubation time of ergotamine resulted in a parallel shift to the left of the curve. The response to ergotamine was inhibited by methyserigide and piperoxan. Incubation with ergotamine resulted in a decrease of the pD2-value of 5-HT together with a marked suppression of the maximum of the 5-HT curve. The response to ACh was affected in accordance with the prediction of an action of ACh and ergotamine on different receptors. The prolonged receptor stimulation by 5-HT or ACh resulted in a decrease of the apparent affinity towards their receptors. Incubation with ACh resulted in a parallel shift to the right of the 5-HT curve. However no inconsistency with the theoretical prediction of an action on separate receptors was observed with the ACh curve in the presence of 5-HT. It is concluded that ergotamine is a partial agonist on the D-tryptamine receptors of tbe isolated rat stomach. The marked decrease of the maximum of the 5-HT curve by ergotamine is probably caused by the slowly reversible character of its antagonism. The parallel shift to the left of the ergotamine curve with the extension of the incubation time and the persistence of its antagonism both are probably caused by a slow diffusion into and from the biophase.
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D004146:Dioxanes / Q000494:pharmacology; D004347:Drug Interactions; D004878:Ergotamine / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009129:Muscle Tonus / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D012701:Serotonin / Q000494:pharmacology*; D013270:Stomach / Q000187:drug effects*; D014363:Tryptamines / Q000494:pharmacology
D004146:Dioxanes; D010880:Piperidines; D014363:Tryptamines; D012701:Serotonin; D000109:Acetylcholine; D004878:Ergotamine