M 3 muscarinic acetylcholine receptor plays a critical role in parasympathetic control of salivation in mice

作者：Takeshi Nakamura, M. Matsui, Keiko Uchida, Akira Futatsugi, Shinji Kusakawa, Nagisa Matsumoto, Kyoko Nakamura, Toshiya Manabe, Makoto M. Taketo, Katsuhiko Mikoshiba · 发表于：The Journal of Physiology · 年份：2004 · DOI：10.1113/jphysiol.2004.064626 · 被引用次数：192 · 研究领域：Salivary Gland Disorders and Functions、Neuropeptides and Animal Physiology、Ion channel regulation and function

The M(1) and M(3) subtypes are the major muscarinic acetylcholine receptors in the salivary gland and M(3) is reported to be more abundant. However, despite initial reports of salivation abnormalities in M(3)-knockout (M(3)KO) mice, it is still unclear which subtype is functionally relevant in physiological salivation. In the present study, salivary secretory function was examined using mice lacking specific subtype(s) of muscarinic receptor. The carbachol-induced [Ca(2+)](i) increase was markedly impaired in submandibular gland cells from M(3)KO mice and completely absent in those from M(1)/M(3)KO mice. This demonstrates that M(3) and M(1) play major and minor roles, respectively, in the cholinergically induced [Ca(2+)](i) increase. Two-dimensional Ca(2+)-imaging analysis revealed the patchy distribution of M(1) in submandibular gland acini, in contrast to the ubiquitous distribution of M(3). In vivo administration of a high dose of pilocarpine (10 mg kg(-1), s.c.) to M(3)KO mice caused salivation comparable to that in wild-type mice, while no salivation was induced in M(1)/M(3)KO mice, indicating that salivation in M(3)KO mice is caused by an M(1)-mediated [Ca(2+)](i) increase. In contrast, a lower dose of pilocarpine (1 mg kg(-1), s.c.) failed to induce salivation in M(3)KO mice, but induced abundant salivation in wild-type mice, indicating that M(3)-mediated salivation has a lower threshold than M(1)-mediated salivation. In addition, M(3)KO mice, but not M(1)KO mice, had ...