Submitted on April 26, 2006
Accepted on July 11, 2006
M2 and M3 muscarinic receptors are involved in enteric nerve-mediated contraction of the mouse ileum: findings obtained using muscarinic receptor knockout mouse
Tadayoshi Takeuchi1*, Keisuke Tanaka2, Hidemitsu Nakajima2, Minoru Matsui3, and Yasu-Taka Azuma2
1 Veterinary Pharmacology, Osaka Prefecture University, Sakai, Japan
2 Veterinary Pharmacology, Osaka Prefecture University, Sakai, Osaka, Japan
3 Basic Medical Sciecnces, University of Tokyo, The Institute of Medical Science, Tokyo, Tokyo, Japan
* To whom correspondence should be addressed. E-mail: takeuchi{at}vet.osakafu-u.ac.jp.
The involvement of muscarinic receptors in neurogenic responses of the ileum was studied in wild-type and muscarinic receptor (M receptor) knockout (KO) mice. Electrical field stimulation (EFS) to the wild-type mouse ileum induced a bi-phasic response, phasic and sustained contraction that was abolished by tetrodotoxin. The sustained contraction was prolonged for an extended period after the termination of EFS. The phasic contraction was completely inhibited by atropine. In contrast, the sustained contraction was enhanced by atropine. Ileal strips prepared from M2 receptor KO mice exhibited a similar phasic contraction as that seen in wild-type mice and a sustained contraction that was larger than that in wild-type mice. In M3 receptor KO mice, a phasic contraction was smaller than that observed in wild-type mice. Acetylcholine exogenously administrated induced concentration-dependent contractions in strips isolated from wild-type, M2 and M3 receptor KO mice. However, contractions in M3 receptor KO mice shifted to the right. The sustained contraction was inhibited by capsaicin and neurokinin NK2 receptor antagonist, suggesting that it is mediated by substance P (SP). SP-induced contraction of M2 receptor KO mice did not differ from that of wild-type mice. SP immunoreactivity was located in enteric neurons, co-localized with M2 receptor immunoreactivity. These results suggest that atropine-sensitive phasic contraction is mainly mediated via the M3 receptor, and SP-mediated sustained contraction is negatively regulated by the M2 receptor at a presynaptic level.
