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  Hiromu Kawasaki¹  Yukako Hatanaka¹  Yukiko Iwatani¹ 

[1] Department of Clinical Pharmaceutical Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-naka, Okayama 700-8530, Japan;

DOI  :  

来源: DOAJ

【 摘 要 】

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 (α 1adrenoceptor agonist), perfusion of lafutidine (0.1 –10 μ M) 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 μ M) 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 μ M) or capsazepine (5 μ M), 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. Keywords:: lafutidine, calcitonin gene-related peptide (CGRP)ergic nerve-mediated vasodilation, vanilloid receptor-1, mesenteric resistance artery (rat)

【 授权许可】

Unknown