{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T23:17:43Z","timestamp":1791501463246,"version":"4.3.4"},"reference-count":55,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2004,7,9]],"date-time":"2004-07-09T00:00:00Z","timestamp":1089331200000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2004,7]]},"abstract":"<jats:p>\n                    The M\n                    <jats:sub>1<\/jats:sub>\n                    and M\n                    <jats:sub>3<\/jats:sub>\n                    subtypes are the major muscarinic acetylcholine receptors in the salivary gland and M\n                    <jats:sub>3<\/jats:sub>\n                    is reported to be more abundant. However, despite initial reports of salivation abnormalities in M\n                    <jats:sub>3<\/jats:sub>\n                    \u2010knockout (M\n                    <jats:sub>3<\/jats:sub>\n                    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\u2010induced [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>i<\/jats:sub>\n                    increase was markedly impaired in submandibular gland cells from M\n                    <jats:sub>3<\/jats:sub>\n                    KO mice and completely absent in those from M\n                    <jats:sub>1<\/jats:sub>\n                    \/M\n                    <jats:sub>3<\/jats:sub>\n                    KO mice. This demonstrates that M\n                    <jats:sub>3<\/jats:sub>\n                    and M\n                    <jats:sub>1<\/jats:sub>\n                    play major and minor roles, respectively, in the cholinergically induced [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>i<\/jats:sub>\n                    increase. Two\u2010dimensional Ca\n                    <jats:sup>2+<\/jats:sup>\n                    \u2010imaging analysis revealed the patchy distribution of M\n                    <jats:sub>1<\/jats:sub>\n                    in submandibular gland acini, in contrast to the ubiquitous distribution of M\n                    <jats:sub>3<\/jats:sub>\n                    .\n                    <jats:italic>In vivo<\/jats:italic>\n                    administration of a high dose of pilocarpine (10 mg kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    ,\n                    <jats:sc>s.c.<\/jats:sc>\n                    ) to M\n                    <jats:sub>3<\/jats:sub>\n                    KO mice caused salivation comparable to that in wild\u2010type mice, while no salivation was induced in M\n                    <jats:sub>1<\/jats:sub>\n                    \/M\n                    <jats:sub>3<\/jats:sub>\n                    KO mice, indicating that salivation in M\n                    <jats:sub>3<\/jats:sub>\n                    KO mice is caused by an M\n                    <jats:sub>1<\/jats:sub>\n                    \u2010mediated [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>i<\/jats:sub>\n                    increase. In contrast, a lower dose of pilocarpine (1 mg kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    ,\n                    <jats:sc>s.c.<\/jats:sc>\n                    ) failed to induce salivation in M\n                    <jats:sub>3<\/jats:sub>\n                    KO mice, but induced abundant salivation in wild\u2010type mice, indicating that M\n                    <jats:sub>3<\/jats:sub>\n                    \u2010mediated salivation has a lower threshold than M\n                    <jats:sub>1<\/jats:sub>\n                    \u2010mediated salivation. In addition, M\n                    <jats:sub>3<\/jats:sub>\n                    KO mice, but not M\n                    <jats:sub>1<\/jats:sub>\n                    KO mice, had difficulty in eating dry food, as shown by frequent drinking during feeding, suggesting that salivation during eating is mediated by M\n                    <jats:sub>3<\/jats:sub>\n                    and that M\n                    <jats:sub>1<\/jats:sub>\n                    plays no practical role in it. These results show that the M\n                    <jats:sub>3<\/jats:sub>\n                    subtype is essential for parasympathetic control of salivation and a reasonable target for the drug treatment and gene therapy of xerostomia, including Sj\u00f6gren's syndrome.\n                  <\/jats:p>","DOI":"10.1113\/jphysiol.2004.064626","type":"journal-article","created":{"date-parts":[[2004,5,17]],"date-time":"2004-05-17T20:44:06Z","timestamp":1084826646000},"page":"561-575","source":"Crossref","is-referenced-by-count":175,"title":["M\n                    <sub>3<\/sub>\n                    muscarinic acetylcholine receptor plays a critical role in parasympathetic control of salivation in mice"],"prefix":"10.1113","volume":"558","author":[{"given":"Takeshi","family":"Nakamura","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minoru","family":"Matsui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiko","family":"Uchida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Futatsugi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinji","family":"Kusakawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nagisa","family":"Matsumoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyoko","family":"Nakamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiya","family":"Manabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto M.","family":"Taketo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuhiko","family":"Mikoshiba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2004,7,9]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.1996.42748.x"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1993.tb18338.x"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1159\/000061125"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1999.276.4.C788"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0003-9969(99)90016-X"},{"key":"e_1_2_5_7_1","first-page":"718","article-title":"Molecular and pharmacological characterization of muscarinic receptor subtypes in a rat parotid gland cell line: comparison with native parotid gland","volume":"297","author":"Bockman CS","year":"2001","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_5_8_1","first-page":"134","article-title":"Differential coupling of m1, m2 and m3 muscarinic receptor subtypes to inositol 1,4,5\u2010trisphosphate and adenosine 3\u2032,5\u2032\u2010cyclic monophosphate accumulation in Chinese hamster ovary cells","volume":"274","author":"Burford NT","year":"1995","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.2003.02588.x"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0163-7258(93)90027-B"},{"key":"e_1_2_5_11_1","first-page":"279","article-title":"International union of pharmacology. 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