{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T12:59:55Z","timestamp":1761742795315},"reference-count":26,"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>\u2003Bladder smooth muscle sensitivity to muscarinic agonists is increased in the overactive bladder. Treatment of rats with streptozotocin induces a diabetic state in which the bladder muscle is overactive and also supersensitive to muscarinic agonists. This study has examined bladder contraction, muscarinic receptor density and receptor\/G\u2010protein coupling in the streptozotocin\u2010induced overactive bladder of the rat.<\/jats:p><jats:p> <jats:bold>2<\/jats:bold>\u2003Diabetes was induced by a single intraperitoneal dose of streptozotocin. Seven days later contraction of isolated detrusor muscle strips was assessed in tissue bath experiments, while receptor density was assayed in saturation experiments with [<jats:sup>3<\/jats:sup>H]\u2010QNB (quinuclidinyl benzilate, <jats:sc>l<\/jats:sc>\u2010[benzilic\u20104,4\u2032\u2010<jats:sup>3<\/jats:sup>H]) and receptor\/G\u2010protein coupling was determined in agonist displacement experiments with this radioligand.<\/jats:p><jats:p> <jats:bold>3<\/jats:bold>\u2003Isolated detrusor strips from diabetic animals displayed an enhanced degree of spontaneous activity (0.060\u2003\u00b1\u20030.016\u2003g\u2003mg<jats:sup>\u22121<\/jats:sup>, compared with 0.015\u2003\u00b1\u20030.004\u2003g\u2003mg<jats:sup>\u22121<\/jats:sup>, <jats:italic>P<\/jats:italic>\u2003&lt;\u20030.05). Carbachol produced contractile responses in tissues from both control and diabetic rats, but the diabetic tissues were more sensitive to this agonist, the pEC<jats:sub>50<\/jats:sub> being 6.52\u2003\u00b1\u20030.17 compared with 5.93\u2003\u00b1\u20030.06 in controls (<jats:italic>P<\/jats:italic>\u2003&lt;\u20030.001). Maximum responses to carbachol were similar in both groups of animals. The increase in carbachol potency was accompanied by a 40% increase in receptor density from 158\u2003\u00b1\u20035 to 221\u2003\u00b1\u200322\u2003fmol\u2003mg<jats:sup>\u22121<\/jats:sup> protein (<jats:italic>P<\/jats:italic>\u2003&lt;\u20030.05), but this was not enough to fully account for the change in tissue sensitivity.<\/jats:p><jats:p> <jats:bold>4<\/jats:bold>\u2003In the absence of GTP\u2010<jats:italic>\u03b3<\/jats:italic>\u2010S, carbachol displaced [<jats:sup>3<\/jats:sup>H]\u2010QNB from two binding sites, the high\u2010affinity site (p<jats:italic>K<\/jats:italic><jats:sub>i<\/jats:sub>\u2003=\u20037.06\u2003\u00b1\u20030.26) which represents the receptors coupled to G\u2010proteins made up 43.1\u2003\u00b1\u20035.9% of the total binding sites in control tissues and this value was similar (41.0\u2003\u00b1\u20034.0%) in the diabetic tissues (p<jats:italic>K<\/jats:italic><jats:sub>i<\/jats:sub>\u2003=\u20036.64\u2003\u00b1\u20030.31). In the presence of GTP\u2010<jats:italic>\u03b3<\/jats:italic>\u2010S, carbachol displaced [<jats:sup>3<\/jats:sup>H]\u2010QNB from a single binding site which had a low\u2010affinity, similar to the low\u2010affinity site observed in the absence of GTP\u2010<jats:italic>\u03b3<\/jats:italic>\u2010S.<\/jats:p><jats:p> <jats:bold>5<\/jats:bold>\u2003These data demonstrate that detrusor supersensitivity is observed after only 1\u2003week of untreated diabetes in the rat. The overactivity is associated with an enhanced sensitivity to carbachol, which is partly explained by an increase in receptor density, but there appears to be no change in receptor\/G\u2010protein coupling.<\/jats:p>","DOI":"10.1111\/j.1474-8673.2006.00371.x","type":"journal-article","created":{"date-parts":[[2006,6,19]],"date-time":"2006-06-19T10:08:50Z","timestamp":1150711730000},"page":"303-309","source":"Crossref","is-referenced-by-count":30,"title":["Muscarinic receptor function, density and G\u2010protein coupling in the overactive diabetic rat bladder"],"prefix":"10.1111","volume":"26","author":[{"given":"L. A.","family":"Stevens","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D. J.","family":"Sellers","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N. G.","family":"McKay","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C. R.","family":"Chapple","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Chess\u2010Williams","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,6,19]]},"reference":[{"key":"e_1_2_5_2_1","first-page":"531","article-title":"Altered muscarinic receptor properties and function in the heart in diabetes","volume":"242","author":"CARRIER G.O.","year":"1987","journal-title":"J. Pharmacol. Exp. 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