{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:30:18Z","timestamp":1792798218486,"version":"4.5.0"},"reference-count":30,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2015,6,8]],"date-time":"2015-06-08T00:00:00Z","timestamp":1433721600000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["23592745"],"award-info":[{"award-number":["23592745"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"name":"HAITEKU from the Ministry of Education, Culture, Sports, Science, and Technology of Japan,","award":["non"],"award-info":[{"award-number":["non"]}],"id":[{"id":"https:\/\/ror.org\/048rj2z13","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2015,6]]},"abstract":"\n New Findings<\/jats:title>\n \n \n \n \n What is the central question of this study?<\/jats:bold>\n <\/jats:p>\n \n Pilocarpine stimulates salivary secretion via muscarinic ACh receptors (mAChRs), although the Ca\n 2+<\/jats:sup>\n \u2010mobilizing effect of pilocarpine in salivary gland cells is extremely small. Therefore, we examined the effect of pilocarpine on Ca\n 2+<\/jats:sup>\n responses in submandibular gland cells and on secretion\n in vitro<\/jats:italic>\n and\n in vivo<\/jats:italic>\n .\n <\/jats:p>\n <\/jats:list-item>\n \n \n What is the main finding and its importance?<\/jats:bold>\n <\/jats:p>\n \n Pilocarpine induces small Ca\n 2+<\/jats:sup>\n responses and reduces the effects of other mAChR agonists on Ca\n 2+<\/jats:sup>\n responses via its partial agonistic effects. These effects of pilocarpine on Ca\n 2+<\/jats:sup>\n responses in the submandibular gland were further established\n in vivo<\/jats:italic>\n with a novel Ca\n 2+<\/jats:sup>\n imaging system and a genetically encoded Ca\n 2+<\/jats:sup>\n indicator.\n <\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>\n \n \n \n Pilocarpine stimulates salivary secretion via muscarinic ACh receptors (mAChRs), although the effect of pilocarpine on Ca\n 2+<\/jats:sup>\n responses in dispersed salivary gland cells is extremely small. Here, we demonstrate the effect of pilocarpine on Ca\n 2+<\/jats:sup>\n responses and salivary secretion in the rat submandibular gland (SMG). In fura\u20102\u2010loaded SMG cells, the maximal effect of pilocarpine on [Ca\n 2+<\/jats:sup>\n ]\n i<\/jats:sub>\n elevation was 16% of that of carbachol, and pilocarpine attenuated carbachol\u2010 and bethanechol (Bet)\u2010induced [Ca\n 2+<\/jats:sup>\n ]\n i<\/jats:sub>\n increases, indicating that pilocarpine acts as a partial agonist for mAChR\u2010mediated Ca\n 2+<\/jats:sup>\n responses. The partial agonistic effect of pilocarpine on Ca\n 2+<\/jats:sup>\n dynamics in the SMG was also confirmed in live animals using the genetically encoded Ca\n 2+<\/jats:sup>\n indicator, YC\u2010Nano50. Administration of pilocarpine (3\u00a0mg\u00a0kg\n \u22121<\/jats:sup>\n ,\n i.p.<\/jats:sc>\n ) elicited a small increase in [Ca\n 2+<\/jats:sup>\n ]\n i<\/jats:sub>\n in the SMG. Quantitative analyses demonstrated that resting [Ca\n 2+<\/jats:sup>\n ]\n i<\/jats:sub>\n was \u223c37\u00a0n\n m<\/jats:sc>\n , which was increased by pilocarpine (3\u00a0mg\u00a0kg\n \u22121<\/jats:sup>\n ) and Bet (10\u00a0mg\u00a0kg\n \u22121<\/jats:sup>\n ) to 44 and 69\u00a0n\n m<\/jats:sc>\n , respectively. The inhibitory effects of pilocarpine on Bet\u2010induced Ca\n 2+<\/jats:sup>\n responses were also elucidated\n in vivo<\/jats:italic>\n . We further examined real\u2010time changes in pilocarpine\u2010induced SMG salivary secretion and showed that pilocarpine induced an extremely weak secretory response and reduced Bet\u2010induced secretion. Unlike Ca\n 2+<\/jats:sup>\n responses, pilocarpine failed to reduce the effect of Bet on SMG blood flow. Our results demonstrate that pilocarpine acts as a partial agonist of mAChRs to induce weak salivary secretion that is correlated with small increases in [Ca\n 2+<\/jats:sup>\n ]\n i<\/jats:sub>\n . Furthermore, pilocarpine exhibits an antagonistic effect on mAChR\u2010induced Ca\n 2+<\/jats:sup>\n responses and salivary secretion.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1113\/ep085110","type":"journal-article","created":{"date-parts":[[2015,4,17]],"date-time":"2015-04-17T06:35:48Z","timestamp":1429252548000},"page":"640-651","source":"Crossref","is-referenced-by-count":13,"title":["Partial agonistic effects of pilocarpine on Ca\n 2+<\/sup>\n responses and salivary secretion in the submandibular glands of live animals"],"prefix":"10.1113","volume":"100","author":[{"given":"Akihiro","family":"Nezu","sequence":"first","affiliation":[{"name":"Department of Pharmacology, School of Dentistry Health Sciences University of Hokkaido Ishikari\u2010Tobetsu Hokkaido 061\u20100293 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takao","family":"Morita","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Dentistry Health Sciences 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