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Investigation of the 5‐hydroxytryptamine receptor mechanism mediating the short‐circuit current response in rat colon
Author(s) -
Bunce K.T.,
Elswood C.J.,
Ball M.T.
Publication year - 1991
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1991.tb12257.x
Subject(s) - methysergide , ketanserin , metoclopramide , cisapride , medicine , endocrinology , agonist , receptor antagonist , chemistry , 5 ht receptor , sulpiride , pharmacology , mechanism of action , receptor , serotonin , antagonist , biology , in vitro , biochemistry , vomiting
1 5‐Hydroxytryptamine (5‐HT) stimulated an increase in short‐circuit current (SCC) in rat isolated colonic mucosa with an EC 50 value of approximately 4 μ m . The purpose of the present study was to investigate the 5‐HT receptor mechanism(s) involved in this response. 2 The relatively selective 5‐HT receptor agonists 5‐carboxamidotryptamine (5‐CT) and α‐methyl‐5‐HT stimulated SCC and were 6 to 8 times less potent than 5‐HT. 2‐Methyl‐5‐HT was inactive both as an agonist and an antagonist. 3 The following compounds produced no significant inhibition of the SCC response to 5‐HT: ketanserin (1 μ m ), methysergide (1 μ m ), methiothepin (0.3 μ m ), GR38032F (0.3 μ m ), tetrodotoxin (0.3 μ m ) and sulpiride (1 μ m ). 4 Both metoclopramide (3 and 10 μ m ) and cisapride (0.1 and 1 μ m ) inhibited the SCC responses to 5‐HT in a concentration‐related manner, and the higher doses similarly inhibited the responses to 5‐CT. With both agonists the inhibitory effects of metoclopramide and cisapride were insurmountable. However, these inhibitory actions appeared to be selective since neither metoclopramide nor cisapride affected the basal SCC or the SCC response to prostaglandin E 2 . 5 The SCC responses to 5‐HT and 5‐methoxytryptamine were selectively inhibited by ICS205‐930 at 3 μ m , and respective pK B values of 6.0 and 6.6 were calculated. 6 It is concluded that 5‐HT stimulates an SCC response in rat colon via a receptor mechanism that cannot be clearly identified as 5‐HT 1 ‐like, 5‐HT 2 or 5‐HT 3 . This receptor is selectively antagonized by ICS205‐930 and by the benzamides, metoclopramide and cisapride. The 5‐HT receptor in rat colon therefore exhibits some of the properties associated with the so‐called 5‐HT 4 receptor.