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Lack of effect of sumatriptan and UK‐14,304 on capsaicin‐induced relaxation of guinea‐pig isolated basilar artery
Author(s) -
O'Shaughnessy C.T.,
Waldron G.J.,
Connor H.E.
Publication year - 1993
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.1476-5381.1993.tb13461.x
Subject(s) - capsaicin , calcitonin gene related peptide , agonist , endocrinology , ruthenium red , medicine , chemistry , sumatriptan , pharmacology , antagonist , guinea pig , nk1 receptor antagonist , substance p , neuropeptide , receptor , calcium
1 The objectives of this study were to assess the effects of sensory neuropeptide antagonists and presynaptically acting receptor agonists on capsaicin‐induced relaxations of guinea‐pig isolated basilar artery (GPBA). 2 Capsaicin, human α‐calcitonin gene‐related peptide (CGRP) and substance P (SP) caused concentration‐related relaxations of GPBA which had been pre‐contracted with prostaglandin F 2α (PGF 2α ). Responses to capsaicin were not modified by the peptidase inhibitors, phosphoramidon (1 μ m ) and bestatin (100 μ m ). 3 The relaxant responses to capsaicin were blocked in a selective manner by ruthenium red (3 μ m ) and by the CGRP antagonist, CGRP 8 _ 37 (1 μ m ). CGRP 8 _ 37 also selectively inhibited the relaxant effects of CGRP. 4 The selective NK 1 receptor antagonist, GR82334 (10 μ m ), inhibited SP‐induced relaxations but had little effect on capsaicin‐induced relaxations. 5 The 5‐HT 1 receptor agonist, sumatriptan, produced small contractions of GPBA under conditions of resting tone. In the presence of PGF 2α , sumatriptan had no further contractile effect. Sumatriptan (0.3 and 3 μ m ) did not modify capsaicin‐induced relaxations of GPBA. 6 The α 2 ‐adrenoceptor agonist, UK‐14,304 (0.1 μ m ), had no effect on basal or PGF 2α ‐induced tone. UK‐14,304 did not modify capsaicin‐induced relaxations. 7 These results suggest that capsaicin causes relaxation of GPBA via a release of CGRP. This process is amenable to blockade by CGRP 8–37 and ruthenium red, but not to modulation by either sumatriptan or UK‐14,304.