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

• Published in: Journal of Pharmacological Sciences 2008, Vol.106(3), pp.505-511
• Main Authors: Sugiyama, Tetsuhiro, Hatanaka, Yukako, Iwatani, Yukiko, Jin, Xin, Kawasaki, Hiromu
• Format: Article
• Language: English
• Subjects: Acetamides - pharmacology; Animals; calcitonin gene-related peptide (CGRP)ergic nerve-mediated vasodilation; Calcitonin Gene-Related Peptide - pharmacology; Capsaicin - analogs & derivatives; Capsaicin - pharmacology; Drug Synergism; Electric Stimulation; lafutidine; Male; Mesenteric Arteries - drug effects; Mesenteric Arteries - physiology; mesenteric resistance artery (rat); Peripheral Nervous System - physiology; Piperidines - pharmacology; Pyridines - pharmacology; Rats; Rats, Wistar; Ruthenium Red - pharmacology; TRPV Cation Channels - physiology; vanilloid receptor-1; Vasodilation - drug effects
• ISSN: 1347-8613; 1347-8648
• DOI: 10.1254/jphs.FP0072259

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 (α1adrenoceptor 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.