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.

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.

Citation

Hayato Matsuyama, Yasuyuki Tanahashi, Takio Kitazawa, Masahisa Yamada, Seiichi Komori, Toshihiro Unno. 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. 2013;121(3):227-36

Mesh Tags

Substances

PMID: 23446189

search → result