{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T01:20:27Z","timestamp":1771550427434,"version":"3.50.1"},"reference-count":31,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2013,5,20]],"date-time":"2013-05-20T00:00:00Z","timestamp":1369008000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int J of Urology"],"published-print":{"date-parts":[[2014,1]]},"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>To investigate whether 7\u2010[2\u2010[4\u2010(2\u2010chlorophenyl) piperazinyl] ethyl]\u20101,3\u2010di\u2010methylxanthine (<jats:styled-content style=\"fixed-case\">KMUP<\/jats:styled-content>\u20101) inhibits the effects of testosterone on the development of benign prostatic hyperplasia and sensitizes prostate contraction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A benign prostatic hyperplasia animal model was established by subcutaneous injections of testosterone (3\u2009mg\/kg\/day, s.c.) for 4 weeks in adult male <jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>prague\u2013<jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>awley rats. Animals were divided into six groups: control, testosterone, testosterone with <jats:styled-content style=\"fixed-case\">KMUP<\/jats:styled-content>\u20101 (2.5, 5\u2009mg\/kg\/day), sildenafil (5\u2009mg\/kg\/day) or doxazosin (5\u2009mg\/kg\/day). After 4 weeks, the animals were killed, and prostate tissues were prepared for isometric tension measurement and western blotting analysis. KMUP\u20101, <jats:styled-content style=\"fixed-case\">Y<\/jats:styled-content>27632, zaprinast, doxazosin or tamsulosin were used at various concentrations to determine the contractility sensitized by phenylephrine (10\u2009\u03bcmol\/L).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">KMUP<\/jats:styled-content>\u20101 inhibited testosterone\u2010induced phosphorylation of extracellular signal\u2010regulated phosphorylated protein kinase and mitogen\u2010activated protein kinase kinase and <jats:styled-content style=\"fixed-case\">R<\/jats:styled-content>ho kinase\u2010<jats:styled-content style=\"fixed-case\">II<\/jats:styled-content> activation. Sildenafil and doxazosin significantly decreased benign prostatic hyperplasia\u2010induced mitogen\u2010activated protein kinase kinase and <jats:styled-content style=\"fixed-case\">R<\/jats:styled-content>ho kinase\u2010<jats:styled-content style=\"fixed-case\">II<\/jats:styled-content> activation. The decreased expressions of soluble guanylate cyclase\u2009\u03b1<jats:sub>1<\/jats:sub> was reversed by <jats:styled-content style=\"fixed-case\">KMUP<\/jats:styled-content>\u20101, doxazosin and sildenafil. Soluble guanylate cyclase\u2009\u03b2<jats:sub>1<\/jats:sub> and protein kinase\u2009<jats:styled-content style=\"fixed-case\">G<\/jats:styled-content> were increased by <jats:styled-content style=\"fixed-case\">KMUP<\/jats:styled-content>\u20101, doxazosin, and sildenafil in the testosterone\u2010treated benign prostatic hyperplasia group. Phosphodiesterase\u20105<jats:styled-content style=\"fixed-case\">A<\/jats:styled-content> was increased by testosterone and inhibited by <jats:styled-content style=\"fixed-case\">KMUP<\/jats:styled-content>\u20101 (5\u2009mg\/kg\/day) or sildenafil (5\u2009mg\/kg\/day). <jats:styled-content style=\"fixed-case\">KMUP<\/jats:styled-content>\u20101 inhibited phenylephrine\u2010sensitized prostate contraction of rats treated with testosterone.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Mitogen\u2010activated protein kinase\u20091\/extracellular regulated protein kinases kinase, soluble guanylate cyclase\/cyclic guanosine monophosphate, protein kinase\/protein kinase <jats:styled-content style=\"fixed-case\">G<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">R<\/jats:styled-content>ho kinase\u2010<jats:styled-content style=\"fixed-case\">II<\/jats:styled-content> are related to prostate smooth muscle tone and proliferation induced by testosterone. <jats:styled-content style=\"fixed-case\">KMUP<\/jats:styled-content>\u20101 inhibits testosterone\u2010induced prostate hyper\u2010contractility and mitogen\u2010activated protein kinase\u20091\/extracellular regulated protein kinases kinase\u2010phosphorylation, and it inactivates <jats:styled-content style=\"fixed-case\">R<\/jats:styled-content>ho kinase\u2010<jats:styled-content style=\"fixed-case\">II<\/jats:styled-content> by cyclic guanosine monophosphate, protein kinase and \u03b11<jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>\u2010adenergic blockade. Thus, <jats:styled-content style=\"fixed-case\">KMUP<\/jats:styled-content>\u20101 might be a beneficial pharmacotherapy for benign prostatic hyperplasia.<\/jats:p><\/jats:sec>","DOI":"10.1111\/iju.12195","type":"journal-article","created":{"date-parts":[[2013,5,21]],"date-time":"2013-05-21T01:02:48Z","timestamp":1369098168000},"page":"87-92","source":"Crossref","is-referenced-by-count":4,"title":["Cyclic guanosine monophosphate\u2010enhancing reduces androgenic extracellular regulated protein kinases\u2010phosphorylation\/Rho kinase II\u2010activation in benign prostate hyperplasia"],"prefix":"10.1111","volume":"21","author":[{"given":"Chi\u2010Ming","family":"Liu","sequence":"first","affiliation":[{"name":"Graduate Institute of Medicine Kaohsiung Medical University  Kaohsiung Taiwan"},{"name":"Department of Pharmacology College of Medicine Kaohsiung Medical University  Kaohsiung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ya\u2010Chin","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology College of Medicine Kaohsiung Medical University  Kaohsiung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi\u2010Ching","family":"Lo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology College of Medicine Kaohsiung Medical University  Kaohsiung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin\u2010Nan","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology College of Medicine Kaohsiung Medical University  Kaohsiung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jwu\u2010Lai","family":"Yeh","sequence":"additional","affiliation":[{"name":"Department of Pharmacology College of Medicine Kaohsiung Medical University  Kaohsiung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ing\u2010Jun","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pharmacology College of Medicine Kaohsiung Medical University  Kaohsiung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,5,20]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-2456(02)00263-5"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-410X.1975.tb03947.x"},{"issue":"3","key":"e_1_2_8_4_1","first-page":"937","article-title":"\u03b11\u2010adrenergic receptor subtypes in human detrusor","volume":"160","author":"Malloy BJ","year":"1998","journal-title":"J. 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