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M 3 muscarinic acetylcholine receptor plays a critical role in parasympathetic control of salivation in mice
Author(s) -
Nakamura Takeshi,
Matsui Minoru,
Uchida Keiko,
Futatsugi Akira,
Kusakawa Shinji,
Matsumoto Nagisa,
Nakamura Kyoko,
Manabe Toshiya,
Taketo Makoto M.,
Mikoshiba Katsuhiko
Publication year - 2004
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2004.064626
Subject(s) - pilocarpine , carbachol , muscarinic acetylcholine receptor , endocrinology , submandibular gland , medicine , acetylcholine , chemistry , knockout mouse , in vivo , muscarinic acetylcholine receptor m3 , receptor , salivary gland , saliva , biology , neuroscience , microbiology and biotechnology , epilepsy
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 difficulty in eating dry food, as shown by frequent drinking during feeding, suggesting that salivation during eating is mediated by M 3 and that M 1 plays no practical role in it. These results show that the M 3 subtype is essential for parasympathetic control of salivation and a reasonable target for the drug treatment and gene therapy of xerostomia, including Sjögren's syndrome.