{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T15:57:53Z","timestamp":1761580673424,"version":"3.37.3"},"reference-count":22,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2009,3,12]],"date-time":"2009-03-12T00:00:00Z","timestamp":1236816000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"NIH","award":["R01-DK075728","R01-NS 44992"],"award-info":[{"award-number":["R01-DK075728","R01-NS 44992"]}]},{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurourology and Urodynamics"],"published-print":{"date-parts":[[2009,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>The presence of muscarinic receptors on bladder urothelial cells (BUC), suggests BUC may be a target for antimuscarinics. This study determined whether human BUC are responsive to a muscarinic agonist and if so, whether responses are altered in interstitial cystitis (IC) BUC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Primary urothelial cell cultures were established from cystoscopic biopsies. Normal (NB) and IC BUC were studied using calcium imaging techniques as a means to monitor the response to muscarinic receptor activation with the agonist, carbachol (CCh). Changes in intracellular Ca<jats:sup>2+<\/jats:sup> concentration ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>) were measured with fura\u20102 ratiometric microfluorimetry. Dose\u2013response curves (CCh dose vs. [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>) were measured in IC and NB BUC. Tolterodine was used to confirm the specificity (muscarinic versus nicotinic) of CCh evoked increases in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>CCh induced a dose\u2010dependent increase in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>. Potency and efficacy of CCh was significantly greater in IC BUC. The maximal increase in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> was 136.3\u2009\u00b1\u20095.1% over baseline in 78 cells from 4 IC patients versus 92.4\u2009\u00b1\u20094.8% over baseline in 67 cells from 4 NB subjects (P\u2009&lt;\u20090.01). The EC50 of the evoked increase was 1.10\u2009\u00b1\u20090.14 \u00b5M versus 3.36\u2009\u00b1\u20090.72 \u00b5M (P\u2009&lt;\u20090.01) in BUC from IC and NB controls, respectively. Removal of extracellular calcium or application of tolterodine, abolished CCh evoked increase in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> in IC and NB BUC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The greater sensitivity of IC BUC to CCh suggests that IC patholobiology may also include alterations muscarinic signaling. The physiologic sequelae of muscarinic activation in BUC need to be further investigated. Neurourol. Urodynam. 28:1022\u20131027, 2009. \u00a9 2009 Wiley\u2010Liss, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/nau.20726","type":"journal-article","created":{"date-parts":[[2009,3,12]],"date-time":"2009-03-12T19:33:42Z","timestamp":1236886422000},"page":"1022-1027","source":"Crossref","is-referenced-by-count":14,"title":["Bladder urothelial cells from patients with interstitial cystitis have an increased sensitivity to carbachol"],"prefix":"10.1002","volume":"28","author":[{"given":"Gopal N.","family":"Gupta","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shao\u2010Gang","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael S.","family":"Gold","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toby C.","family":"Chai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,3,12]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ki.5002439"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2006.06.088"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4694-07.2008"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/bjp.2008.6"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00313.2007"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(17)41529-1"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005392-199501000-00085"},{"key":"e_1_2_1_9_2","first-page":"1696","article-title":"Ca2+ mobilization in nontransformed ciliary nonpigmented epithelial cells","volume":"33","author":"Ohuchi T","year":"1992","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2007.01.053"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0706147"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.2174\/138161206778522056"},{"key":"e_1_2_1_13_2","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.108.141788"},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.106.114314"},{"key":"e_1_2_1_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-008-8027-y"},{"key":"e_1_2_1_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn902"},{"key":"e_1_2_1_17_2","doi-asserted-by":"crossref","unstructured":"GuptaGN LiM SunY et al.Increased efficacy and potency of carbachol in inducing increases in intracellular calcium ([Ca2+])i and outward potassium currents (Io) in interstitial cystitis (IC) bladder urothelial cells (BUC): Evidence of persistent phenotypic alteration of culture. 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