title: 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.
abstract: 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.
authors: Laboratory of Pharmacology, Department of Veterinary Medicine, Faculty of Applied Biological Science, Gifu University, Gifu, Japan.
authors: Hayato
authors: H
authors: Matsuyama
authors: Yasuyuki
authors: Y
authors: Tanahashi
authors: Takio
authors: T
authors: Kitazawa
authors: Masahisa
authors: M
authors: Yamada
authors: Seiichi
authors: S
authors: Komori
authors: Toshihiro
authors: T
authors: Unno
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002478:Cells, Cultured; D018118:Chloride Channels / Q000378:metabolism* / Q000502:physiology; D059329:Cholinergic Neurons / Q000502:physiology*; D004558:Electric Stimulation; D005260:Female; D007082:Ileum / Q000166:cytology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009130:Muscle, Smooth / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000502:physiology*; D037342:Pertussis Toxin / Q000494:pharmacology; D043585:Receptor, Muscarinic M2 / Q000502:physiology*; D043587:Receptor, Muscarinic M3 / Q000502:physiology*
chemical_list: D018118:Chloride Channels; D043585:Receptor, Muscarinic M2; D043587:Receptor, Muscarinic M3; D037342:Pertussis Toxin