Lack of effect of sumatriptan and UK‐14,304 on capsaicin‐induced relaxation of guinea‐pig isolated basilar artery

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Abstract
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 F2α (PGF2α). Responses to capsaicin were not modified by the peptidase inhibitors, phosphoramidon (1 μm) and bestatin (100 μm). 3 The relaxant responses to capsaicin were blocked in a selective manner by ruthenium red (3 μm) and by the CGRP antagonist, CGRP8_37 (1 μm). CGRP8_37 also selectively inhibited the relaxant effects of CGRP. 4 The selective NK1 receptor antagonist, GR82334 (10 μm), inhibited SP-induced relaxations but had little effect on capsaicin-induced relaxations. 5 The 5-HT1 receptor agonist, sumatriptan, produced small contractions of GPBA under conditions of resting tone. In the presence of PGF2α, sumatriptan had no further contractile effect. Sumatriptan (0.3 and 3 μm) did not modify capsaicin-induced relaxations of GPBA. 6 The α2-adrenoceptor agonist, UK-14,304 (0.1 μm), had no effect on basal or PGF2α-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 CGRP8–37 and ruthenium red, but not to modulation by either sumatriptan or UK-14,304.