Investigation of the 5-HT receptor mediating relaxation in guinea-pig proximal colon.
5-Hydroxytryptamine (5-HT) induced concentration-related relaxations (EC50 = 9.1 microM) of guinea-pig proximal colon pretreated with ketanserin (1 microM) and ondansetron (10 microM). This 5-HT-induced effect was neuronally mediated since it was blocked by tetrodotoxin (0.3 microM). 5-Carboxamidotryptamine was a full agonist and ten times more potent than 5-HT. alpha-Methyl-5-HT was a partial agonist. 2-Methyl-5-HT was without effect. Methysergide and metergoline were antagonists of 5-HT producing parallel shifts at 0.1 microM but unsurmountable antagonism at higher concentrations. pKB values of 8.0 and 7.3 were calculated for methysergide and metergoline, respectively. This study has identified a 5-HT-induced relaxation of guinea-pig proximal colon which is mediated via a neuronal 5-HT1-like receptor. However, the subtype has yet to be established.
Department of Gastrointestinal Pharmacology, Glaxo Group Research Ltd, Ware, Herts, UK.
C J
CJ
Elswood
K T
KT
Bunce
D000818:Animals; D003106:Colon / Q000187:drug effects / Q000502:physiology; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology; D012702:Serotonin Antagonists / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D012701:Serotonin; D013779:Tetrodotoxin; C047087:5-carboxamidotryptamine