title: Muscarinic acetylcholine receptor M1 and M3 subtypes mediate acetylcholine-induced endothelium-independent vasodilatation in rat mesenteric arteries.
abstract: The present study investigated pharmacological characterizations of muscarinic acetylcholine receptor (AChR) subtypes involving ACh-induced endothelium-independent vasodilatation in rat mesenteric arteries. Changes in perfusion pressure to periarterial nerve stimulation and ACh were measured before and after the perfusion of Krebs solution containing muscarinic receptor antagonists. Distributions of muscarinic AChR subtypes in mesenteric arteries with an intact endothelium were studied using Western blotting. The expression level of M1 and M3 was significantly greater than that of M2. Endothelium removal significantly decreased expression levels of M2 and M3, but not M1. In perfused mesenteric vascular beds with intact endothelium and active tone, exogenous ACh (1, 10, and 100 nmol) produced concentration-dependent and long-lasting vasodilatations. In endothelium-denuded preparations, relaxation to ACh (1 nmol) disappeared, but ACh at 10 and 100 nmol caused long-lasting vasodilatations, which were markedly blocked by the treatment of pirenzepine (M1 antagonist) or 4-DAMP (M1 and M3 antagonist) plus hexamethonium (nicotinic AChR antagonist), but not methoctramine (M2 and M4 antagonist). These results suggest that muscarinic AChR subtypes, mainly M1, distribute throughout the rat mesenteric arteries, and that activation of M1 and/or M3 which may be located on CGRPergic nerves releases CGRP, causing an endothelium-independent vasodilatation.
authors.affiliation: Department of Clinical Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan; Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Panot
authors.initials: P
authors.lastname: Tangsucharit
authors.affiliation: Department of Clinical Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan; Department of Clinical Pharmacy, College of Pharmaceutical Sciences, Matsuyama University, Matsuyama, Ehime, Japan. Electronic address: stakator@cc.matsuyama-u.ac.jp.
authors.forename: Shingo
authors.initials: S
authors.lastname: Takatori
authors.affiliation: Department of Pharmaceutical Care and Health Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Japan.
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Zamami
authors.affiliation: Department of Clinical Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan; Department of Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University, Osaka, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Goda
authors.affiliation: Department of Physiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Poungrat
authors.initials: P
authors.lastname: Pakdeechote
authors.affiliation: Department of Clinical Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan; Department of Clinical Pharmacy, College of Pharmaceutical Sciences, Matsuyama University, Matsuyama, Ehime, Japan.
authors.forename: Hiromu
authors.initials: H
authors.lastname: Kawasaki
authors.affiliation: Department of Clinical Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
authors.forename: Fusako
authors.initials: F
authors.lastname: Takayama
mesh_terms: D000109:Acetylcholine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular; D018738:Hexamethonium / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology; D010890:Pirenzepine / Q000494:pharmacology; D017208:Rats, Wistar; D043643:Receptor, Muscarinic M1 / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D043587:Receptor, Muscarinic M3 / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D010880:Piperidines; D043643:Receptor, Muscarinic M1; D043587:Receptor, Muscarinic M3; D018738:Hexamethonium; D010890:Pirenzepine; C042375:4-diphenylacetoxy-1,1-dimethylpiperidinium; D015740:Calcitonin Gene-Related Peptide; D000109:Acetylcholine
keywords: Acetylcholine-induced vasodilatation; CGRPergic nerves; Muscarinic receptor subtypes; Rat mesenteric arteries