Evidence for M2 and M3 Muscarinic Receptor Involvement in Cholinergic Excitatory Junction Potentials Through Synergistic Activation of Cation Channels in the Longitudinal Muscle of Mouse Ileum

Journal of Pharmacological Sciences

Hayato Matsuyama²  Masahisa Yamada⁴  Yasuyuki Tanahashi¹  Toshihiro Unno²  Seiichi Komori²  Takio Kitazawa³ 

[1] Laboratory of Pharmacology, Department of Animal Medical Sciences, Faculty of Life Sciences, Kyoto Sangyo University, Japan;Laboratory of Pharmacology, Department of Veterinary Medicine, Faculty of Applied Biological Science, Gifu University, Japan;Department of Pharmacology, School of Veterinary Medicine, Rakuno Gakuen University, Japan;Common Resources Group, Okinawa Institute of Science and Technology, Japan

关键词: muscarinic receptor;    smooth muscle;    nonselective cation channel;    excitatory junction potential (EJP);    small intestine;   

DOI  :  10.1254/jphs.12231FP

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(37)Cited-By(3)Cholinergic nerve–mediated excitatory junction potentials (EJPs) in the longitudinal muscle of mouse ileum were characterized by using M2 or M3 muscarinic receptor–knockout (KO) mice and 1-[β-[3-(4-methoxyphenyl) propoxy]-4-methoxyphenethyl]-1H-imidazole hydrochloride (SK&F 96365) and pertussis toxin (PTX). EJPs evoked by electrical field stimulation (EFS) in wild-type preparations, initially determined to be cholinergic in origin using tetrodotoxin, atropine, and eserine, were profoundly depressed after SK&F 96365 treatment known to block muscarinic receptor–operated cation channels. A similar depression of the EJPs was also observed by PTX treatment, which is predicted to disrupt M2-mediated pathways linked to cation channel activation. In M2-KO mouse preparations, cholinergic EJPs were evoked by EFS with their relative amplitude of 20% – 30% to the wild-type EJP and strongly inhibited by SK&F 96365. No cholinergic EJP was seen in M3-KO as well as M2/M3 double-KO preparations. The results suggest that the wild-type cholinergic EJP is not a simple mixture of M2 and M3 responses, but due to synergistic activation of cation channels by both M2 and M3 receptors in the murine ileal longitudinal muscle.

【 授权许可】

Unknown