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An enhancing effect of 5‐hydroxytryptamine on electrically evoked atropine‐resistant contraction of guinea‐pig proximal colon
Author(s) -
Kojima ShuIchi,
Shimo Yasuo
Publication year - 1995
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.1476-5381.1995.tb14907.x
Subject(s) - hexamethonium , ketanserin , antagonist , atropine , endocrinology , receptor antagonist , medicine , chemistry , prazosin , muscle contraction , 5 ht receptor , tachykinin receptor , receptor , contraction (grammar) , guinea pig , pharmacology , substance p , serotonin , neuropeptide
1 In the presence of atropine (0.2 μ m ) and indomethacin (2 μ m ), the effects of 5‐hydroxytryptamine (5‐HT) have been studied on electrically‐evoked, neurogenic contractions of the guinea‐pig proximal colon in vitro . 2 5‐HT, at higher concentrations than 1 n m , caused an increase in electrically (1 Hz, 0.3 ms, 160 mA)‐evoked, atropine‐resistant contractions in a concentration‐dependent manner and at 30 n m produced a maximal effect (pEC 50 value of 8.20 ± 0.11, n = 6). The enhancing effects of 5‐HT on the electrically evoked contractions were mimicked by α‐methyl‐5‐HT (pEC 50 value of 6.59 ± 0.05, n = 6). 3 Both hexamethonium (100 μ m ) and spantide (10 μ m ), selective antagonists for nicotinic and tachykinin receptors respectively, significantly reduced the enhancement of the electrically evoked contractions by 5‐HT (30 n m ). 4 DAU 6285 (3 μ m ), a 5‐HT 4 receptor antagonist, abolished the enhancing action of 5‐HT (30 n m ), but metitepine (0.03 μ m ), a 5‐HT 1 /5‐HT 2 receptor antagonist, ketanserin (0.01 μ m ), a 5‐HT 2 receptor antagonist, and ondansetron (1 μ m ), a 5‐HT 3 receptor antagonist, had no effect on the enhancement. The enhancing effects of a‐methyl‐5‐HT (1 μ m ) were also abolished by DAU 6285 (3 μ m ). 5 Both 5‐HT (30 n m ) and α‐methyl‐5‐HT (1 μ m ) had no effect on contractions to exogenous substance P (0.15–0.3 n m ). 6 These results indicate that in the guinea‐pig proximal colon, 5‐HT produced an enhancement of atropine‐resistant neurogenic contraction induced by electrical field stimulation through pre‐junctional mechanisms and that the enhancement is mediated by the stimulation of 5‐HT 4 receptors located on intramural preganglionic cholinergic neurones and tachykininergic neurones.