title: Histamine H(3) receptor-mediated modulation of perivascular nerve transmission in rat mesenteric arteries.
abstract: The rat mesenteric artery has been shown to be innervated by adrenergic vasoconstrictor nerves and calcitonin gene-related peptide (CGRP)-containing (CGRPergic) vasodilator nerves. The present study was designed to investigate the involvement of histamine H(3) receptors in the neurotransmission of perivascular adrenergic and CGRPergic nerves. The mesenteric vascular beds without an endothelium isolated from male Wistar rats were perfused with Krebs solution and perfusion pressure was measured. In preparations with resting tension, the selective H(3) receptor agonist (R)-α-methylhistamine (α-methylhistamine; 10-100nM) significantly reduced periarterial nerve stimulation (2-8Hz)-induced vasoconstriction and noradrenaline release in the perfusate without an effect on the vasoconstriction induced by exogenously injected noradrenaline (0.5, 1.0nmol). In preparations with active tone produced by methoxamine (2μM) and in the presence of guanethidine (5μM), the periarterial nerve stimulation (1, 2Hz)-induced vasodilator response was inhibited by α-methylhistamine (0.1-1μM) perfusion without affecting vasodilation induced by exogenously injected CGRP (5pmol). Clobenpropit (histamine H(3) receptor antagonist, 1μM) canceled the α-methylhistamine-induced decrease in the periarterial nerve stimulation-induced vasoconstriction and noradrenaline release and periarterial nerve stimulation-induced vasodilation. These results suggest that the stimulation of H(3) receptors located in rat perivascular nerves inhibits presynaptically the neurotransmission of not only adrenergic nerves, but also CGRP nerves, by decreasing neurotransmitters.
authors.affiliation: Department of Clinical Pharmaceutical Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-naka, Okayama 700-8530, Japan.
authors.forename: Pengyuan
authors.initials: P
authors.lastname: Sun
authors.forename: Shingo
authors.initials: S
authors.lastname: Takatori
authors.forename: Xin
authors.initials: X
authors.lastname: Jin
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Koyama
authors.forename: Panot
authors.initials: P
authors.lastname: Tangsucharit
authors.forename: Simin
authors.initials: S
authors.lastname: Li
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Zamami
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Kitamura
authors.forename: Hiromu
authors.initials: H
authors.lastname: Kawasaki
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000008:administration & dosage / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007267:Injections; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000294:innervation* / Q000378:metabolism* / Q000502:physiology; D008761:Methylhistamines / Q000494:pharmacology; D009638:Norepinephrine / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018100:Receptors, Histamine H3 / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D007093:Imidazoles; D008761:Methylhistamines; D018100:Receptors, Histamine H3; C069357:alpha-methylhistamine; D013890:Thiourea; D015740:Calcitonin Gene-Related Peptide; C086108:clobenpropit; D009638:Norepinephrine