{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:36:44Z","timestamp":1790833004077,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":790,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2006,12]]},"abstract":"<jats:sec><jats:title>Background and purpose:<\/jats:title><jats:p>The functional roles of M<jats:sub>2<\/jats:sub>and M<jats:sub>3<\/jats:sub>muscarinic receptors in neurogenic cholinergic contractions in gastrointestinal tracts remain to be elucidated. To address this issue, we studied cholinergic nerve\u2010induced contractions in the ileum using mutant mice lacking M<jats:sub>2<\/jats:sub>or M<jats:sub>3<\/jats:sub>receptor subtypes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental approach:<\/jats:title><jats:p>Contractile responses to transmural electrical (TE) stimulation were isometrically recorded in ileal segments from M<jats:sub>2<\/jats:sub>\u2010knockout (KO), M<jats:sub>3<\/jats:sub>\u2010KO, M<jats:sub>2<\/jats:sub>\/M<jats:sub>3<\/jats:sub>\u2010double KO, and wild\u2010type mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key results:<\/jats:title><jats:p>TE stimulation at 2\u201050 Hz frequency\u2010dependently evoked a fast, brief contraction followed by a slower, longer one in wild\u2010type, M<jats:sub>2<\/jats:sub>\u2010KO or M<jats:sub>3<\/jats:sub>\u2010KO mouse preparations. Tetrodotoxin blocked both the initial and later contractions, while atropine only inhibited the initial contractions. The initial cholinergic contractions were significantly greater in wild\u2010type than M<jats:sub>2<\/jats:sub>\u2010KO or M<jats:sub>3<\/jats:sub>\u2010KO mice; the respective mean amplitudes at 50 Hz were 91, 74 and 68 % of 70mM K<jats:sup>+<\/jats:sup>\u2010induced contraction. Pretreatment with pertussis toxin blocked the cholinergic contractions in M<jats:sub>3<\/jats:sub>\u2010KO but not in M<jats:sub>2<\/jats:sub>\u2010KO mice. Cholinergic contractions also remained in wild\u2010type preparations, but their sizes were reduced by 20\u201030 % at 10\u201050 Hz. In M<jats:sub>2<\/jats:sub>\/M<jats:sub>3<\/jats:sub>\u2010double KO mice, TE stimulation evoked only slow, noncholinergic contractions, which were significantly greater in sizes than in any of the other three mouse strains.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications:<\/jats:title><jats:p>These results demonstrate that M<jats:sub>2<\/jats:sub>and M<jats:sub>3<\/jats:sub>receptors participate in mediating cholinergic contractions in mouse ileum with the latter receptors assuming a greater role. Our data also suggest that the lack of both M<jats:sub>2<\/jats:sub>and M<jats:sub>3<\/jats:sub>receptors causes upregulation of noncholinergic excitatory innervation of the gut smooth muscle.<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic>(2006)<jats:bold>149<\/jats:bold>, 1022\u20131030. doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0706955\">10.1038\/sj.bjp.0706955<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1038\/sj.bjp.0706955","type":"journal-article","created":{"date-parts":[[2006,11,13]],"date-time":"2006-11-13T12:17:31Z","timestamp":1163420251000},"page":"1022-1030","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Roles of M<sub>2<\/sub>and M<sub>3<\/sub>muscarinic receptors in cholinergic nerve\u2010induced contractions in mouse ileum studied with receptor knockout 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