{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T19:18:48Z","timestamp":1761765528106,"version":"3.37.3"},"reference-count":29,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2012,3,6]],"date-time":"2012-03-06T00:00:00Z","timestamp":1330992000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"crossref","award":["20599012, 122591793"],"award-info":[{"award-number":["20599012, 122591793"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurourology and Urodynamics"],"published-print":{"date-parts":[[2012,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>We investigated the relative important role of rho kinase (ROK) and protein kinase C (PKC) pathways in carbachol (CCh)\u2010induced Ca<jats:sup>2+<\/jats:sup> sensitization in \u03b1\u2010toxin permeabilized Guinea pig detrusor smooth muscle (DSM) following bladder outlet obstruction (BOO).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Bladder outlet obstruction was created by placement of a silver jeweler's jump rings loosely round the urethro\u2010vesical junction of Guinea pigs. Sham operated Guinea pig underwent a similar protocol without application of the ring and served as control. \u03b1\u2010Toxin permeabilized DSM strips from control Guinea pigs and those subjected to 6\u20138 weeks of BOO were mounted horizontally for isometric force recording in 100\u2009\u00b5l relaxing solution on perspex block. The effect of ROK inhibitor (Y\u201027632) and PKC inhibitor (GF\u2010109203X) on CCh\u2010induced Ca<jats:sup>2+<\/jats:sup> sensitization was studied during sustained contraction. Permeabilized DSM strips were also stimulated by cumulative increase of Ca<jats:sup>2+<\/jats:sup> concentration compared to that in control in the presence and in the absence of sensitization\u2010induced PKC activator, phorbol 12,13\u2010dibutyrate.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Ca<jats:sup>2+<\/jats:sup> sensitization\u2010induced by CCh was greater in BOO compared to controls. This muscarinic agonist\u2010induced Ca<jats:sup>2+<\/jats:sup> sensitization was inhibited by Y\u201027632 or GF\u2010109203X. The inhibitory effect of Y\u201027632 (5\u2009\u00b5M) was greater while the inhibitory effect of GF\u2010109203X (5\u2009\u00b5M) was smaller in BOO compared to that in controls. Phorbol 12,13\u2010dibutyrate (1\u2009\u00b5M) markedly increased Ca<jats:sup>2+<\/jats:sup> sensitivity in controls but not in BOO.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings provide the first evidence that BOO enhances the ROK pathway and diminishes the PKC pathway in CCh\u2010induced Ca<jats:sup>2+<\/jats:sup> sensitization in contraction of permeabilized Guinea pig DSM and suggest that inhibitors of ROK might potentially relieve bladder dysfunction related to BOO. Neurourol. Urodynam. 31:593\u2013599, 2012. \u00a9 2012 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/nau.21193","type":"journal-article","created":{"date-parts":[[2012,3,6]],"date-time":"2012-03-06T17:23:52Z","timestamp":1331054632000},"page":"593-599","source":"Crossref","is-referenced-by-count":8,"title":["Obstruction enhances rho\u2010kinase pathway and diminishes protein kinase C pathway in carbachol\u2010induced calcium sensitization in contraction of \u03b1\u2010toxin permeabilized guinea pig detrusor smooth muscle"],"prefix":"10.1002","volume":"31","author":[{"given":"Nouval","family":"Shahab","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shunichi","family":"Kajioka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fumi","family":"Takahashi\u2010Yanaga","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mitsuho","family":"Onimaru","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miho","family":"Matsuda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Narihito","family":"Seki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seiji","family":"Naito","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,3,6]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(17)49698-4"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/nau.20475"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/372231a0"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00023.2003"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.273.5272.245"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(97)00657-1"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(01)66826-5"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.ju.0000130419.32165.6b"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-012078160-7\/50018-4"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.103.063735"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0706723"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(17)38477-X"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00378.2002"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/nau.20588"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00117.2004"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-201X.1998.tb10698.x"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3205(86)90529-1"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/40187"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/nau.20625"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)98476-0"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00095.2009"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1128"},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20021040"},{"key":"e_1_2_7_25_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2002.029306"},{"key":"e_1_2_7_26_2","doi-asserted-by":"publisher","DOI":"10.1080\/03008880410015147"},{"key":"e_1_2_7_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2009.38"},{"key":"e_1_2_7_28_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.jbchem.a124993"},{"key":"e_1_2_7_29_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0307812101"},{"key":"e_1_2_7_30_2","doi-asserted-by":"publisher","DOI":"10.1002\/nau.20122"}],"container-title":["Neurourology 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