Lafutidine Facilitates Calcitonin Gene-Related Peptide (CGRP) Nerve-Mediated Vasodilation via Vanilloid-1 Receptors in Rat Mesenteric Resistance Arteries

Journal of Pharmacological Sciences

Tetsuhiro Sugiyama¹  Xin Jin¹  Yukiko Iwatani¹  Hiromu Kawasaki¹  Yukako Hatanaka¹ 

[1] Department of Clinical Pharmaceutical Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Japan

关键词: lafutidine;    calcitonin gene-related peptide (CGRP)ergic nerve-mediated vasodilation;    vanilloid receptor-1;    mesenteric resistance artery (rat);   

DOI  :  10.1254/jphs.FP0072259

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(19)Cited-By(4)Lafutidine is a histamine H2-receptor antagonist with gastric antisecretory and gastroprotective activity associated with activation of capsaicin-sensitive nerves. The present study examined the effect of lafutidine on neurotransmission of capsaicin-sensitive calcitonin gene-related peptide (CGRP)-containing vasodilator nerves (CGRPergic nerves) in rat mesenteric resistance arteries. Rat mesenteric vascular beds were perfused with Krebs solution and vascular endothelium was removed by 30-s perfusion with sodium deoxycholate. In preparations preconstricted by continuous perfusion of methoxamine (α1 adrenoceptor agonist), perfusion of lafutidine (0.1 – 10 μM) concentration-dependently augmented vasodilation induced by the periarterial nerve stimulation (PNS, 1 Hz) without affecting vasodilation induced by exogenous CGRP (10 pmol) injection. Perfusion of famotidine (H2-receptor antagonist, 1 – 100 μM) had no effect on either PNS-induced or CGRP-induced vasodilation. Perfusion of lafutidine concentration-dependently augmented vasodilation induced by a bolus injection of capsaicin (vanilloid-1 receptor agonist, 30 pmol). The presence of a vanilloid-1 receptor antagonist, ruthenium red (10 μM) or capsazepine (5 μM), abolished capsaicin-induced vasodilation and significantly decreased the PNS-induced vasodilation. The decreased PNS-induced vasodilation by ruthenium red or capsazepine was not affected by perfusion of lafutidine. These results suggest that lafutidine facilitates CGRP nerve-mediated vasodilation by modulating the function of presynaptic vanilloid-1 receptors located in CGRPergic nerves.

【 授权许可】

Unknown