{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T01:10:49Z","timestamp":1787793049188,"version":"build-2784847793"},"reference-count":47,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2006,6,19]],"date-time":"2006-06-19T00:00:00Z","timestamp":1150675200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Auton Autocoid Pharmacol"],"published-print":{"date-parts":[[2006,7]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p><jats:bold>1<\/jats:bold>\u2003The M<jats:sub>3<\/jats:sub>muscarinic receptor subtype is widely accepted as the receptor on smooth muscle cells that mediates cholinergic contraction of the normal urinary bladder and other smooth muscle tissues, however, we have found that the M<jats:sub>2<\/jats:sub>receptor participates in contraction under certain abnormal conditions. The aim of this study was to determine the effects of various experimental pathologies on the muscarinic receptor subtype mediating urinary bladder contraction.<\/jats:p><jats:p><jats:bold>2<\/jats:bold>\u2003Experimental pathologies resulting in bladder hypertrophy (denervation and outlet obstruction) result in an up\u2010regulation of bladder M<jats:sub>2<\/jats:sub>receptors and a change in the receptor subtype mediating contraction from M<jats:sub>3<\/jats:sub>towards M<jats:sub>2<\/jats:sub>. Preventing the denervation\u2010induced bladder hypertrophy by urinary diversion prevents this shift in contractile phenotype indicating that hypertrophy is responsible as opposed to denervation<jats:italic>per se<\/jats:italic>.<\/jats:p><jats:p><jats:bold>3<\/jats:bold>\u2003The hypertrophy\u2010induced increase in M<jats:sub>2<\/jats:sub>receptor density and contractile response is accompanied by an increase in the tissue concentrations of mRNA coding for the M<jats:sub>2<\/jats:sub>receptor subtype, however, M<jats:sub>3<\/jats:sub>receptor protein density does not correlate with changes in M<jats:sub>3<\/jats:sub>receptor tissue mRNA concentrations across different experimental pathologies.<\/jats:p><jats:p><jats:bold>4<\/jats:bold>\u2003This shift in contractile phenotype from M<jats:sub>3<\/jats:sub>towards M<jats:sub>2<\/jats:sub>subtype is also observed in aged male Sprague\u2013Dawley rats but not females or either sex of the Fisher344 strain of rats.<\/jats:p><jats:p><jats:bold>5<\/jats:bold>\u2003Four repeated, sequential agonist concentration response curves also cause this shift in contractile phenotype in normal rat bladder strips<jats:italic>in vitro<\/jats:italic>, as evidenced by a decrease in the affinity of the M<jats:sub>3<\/jats:sub>selective antagonist<jats:italic>p<\/jats:italic>\u2010fluoro\u2010hexahydro\u2010sila\u2010diphenidol (<jats:italic>p<\/jats:italic>\u2010F\u2010HHSiD).<\/jats:p><jats:p><jats:bold>6<\/jats:bold>\u2003A similar decrease in the contractile affinity of M<jats:sub>3<\/jats:sub>selective antagonists (darifenacin and<jats:italic>p<\/jats:italic>\u2010F\u2010HHSiD) is also observed in bladder specimens from patients with neurogenic bladder as well as certain organ transplant donors.<\/jats:p><jats:p><jats:bold>7<\/jats:bold>\u2003It is concluded that although the M<jats:sub>3<\/jats:sub>receptor subtype predominately mediates contraction under normal circumstances, the M<jats:sub>2<\/jats:sub>receptor subtype can take over a contractile role when the M<jats:sub>3<\/jats:sub>subtype becomes inactivated by, for example, repeated agonist exposures or bladder hypertrophy. This finding has substantial implications for the clinical treatment of abnormal bladder contractions.<\/jats:p>","DOI":"10.1111\/j.1474-8673.2006.00377.x","type":"journal-article","created":{"date-parts":[[2006,6,19]],"date-time":"2006-06-19T10:08:50Z","timestamp":1150711730000},"page":"311-325","source":"Crossref","is-referenced-by-count":34,"title":["Regulation of bladder muscarinic receptor subtypes by experimental pathologies"],"prefix":"10.1111","volume":"26","author":[{"suffix":"Sr","given":"M. R.","family":"Ruggieri","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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