title: Lafutidine facilitates calcitonin gene-related peptide (CGRP) nerve-mediated vasodilation via vanilloid-1 receptors in rat mesenteric resistance arteries.
abstract: Lafutidine is a histamine H(2)-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 (alpha(1) adrenoceptor agonist), perfusion of lafutidine (0.1 - 10 microM) 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 (H(2)-receptor antagonist, 1 - 100 microM) 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 microM) or capsazepine (5 microM), 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.
authors.affiliation: Department of Clinical Pharmaceutical Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Japan.
authors.forename: Tetsuhiro
authors.initials: T
authors.lastname: Sugiyama
authors.forename: Yukako
authors.initials: Y
authors.lastname: Hatanaka
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Iwatani
authors.forename: Xin
authors.initials: X
authors.lastname: Jin
authors.forename: Hiromu
authors.initials: H
authors.lastname: Kawasaki
mesh_terms: D000081:Acetamides / Q000494:pharmacology*; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology; D004357:Drug Synergism; D004558:Electric Stimulation; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000502:physiology; D017933:Peripheral Nervous System / Q000502:physiology; D010880:Piperidines / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012430:Ruthenium Red / Q000494:pharmacology; D050916:TRPV Cation Channels / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D000081:Acetamides; D010880:Piperidines; D011725:Pyridines; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D012430:Ruthenium Red; C076948:lafutidine; D015740:Calcitonin Gene-Related Peptide; C071423:capsazepine; D002211:Capsaicin