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Involvement of neurokinins in the non‐cholinergic response to activation of 5‐HT 3 and 5‐HT 4 receptors in guinea‐pig ileum
Author(s) -
Ramírez M.J.,
Cenarruzabeitia E.,
Río J.,
Lasheras B.
Publication year - 1994
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.1476-5381.1994.tb14751.x
Subject(s) - medicine , endocrinology , agonist , neurokinin b , tachykinin receptor , acetylcholine , receptor , myenteric plexus , neurokinin a , atropine , 5 ht receptor , stimulation , chemistry , cholinergic , biology , serotonin , substance p , neuropeptide , immunohistochemistry
1 The involvement of neurokinins in the non‐cholinergically‐mediated contractile response induced by stimulation of 5‐HT 3 and 5‐HT 4 receptors has been examined in the longitudinal muscle‐myenteric plexus preparation of the guinea‐pig ileum. 2 The 5‐HT 3 receptor agonist, 2‐methyl‐5‐hydroxytryptamine (2‐methyl‐5‐HT), showed a lower potency in this preparation than the more selective 5‐HT 4 receptor agonist 5‐methoxytryptamine. The effect of both drugs was markedly reduced by atropine. 3 Substance P (SP) and neurokinin B (NKB) produced biphasic concentration‐response curves in the preparation. Neurokinin A (NKA), the NK 1 receptor agonist, [Sar 9 , Met(O 2 ) 11 ]SP and the NK 3 receptor agonist, senktide yielded monophasic concentration‐response curves. 4 After desensitization of the NK 1 receptor with SP or [Sar 9 , met(O 2 ) 11 ]SP, in the presence of atropine, the contractile response to 2‐methyl‐5‐HT was entirely blocked. Desensitization of NK 3 receptors with NKB, also in the presence of atropine, fully suppressed the 5‐HT 4 receptor‐mediated contraction evoked by 5‐methoxytryptamine. 5 In preparations prelabelled with [ 3 H]‐choline, SP produced a concentration‐dependent increase in tritium overflow, an index of [ 3 H]‐acetylcholine release, while an inverse relationship was found with NKB. At low neurokinin concentrations, the releasing effect of NKB was much more marked. 6 It is suggested that in the response to 5‐HT 3 receptor stimulation, there is a role for SP and acetylcholine. NKB appears to be preferentially involved in the release of acetylcholine elicited by stimulation of 5‐HT 4 receptors.