{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T20:51:33Z","timestamp":1762375893438},"reference-count":12,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2014,10,28]],"date-time":"2014-10-28T00:00:00Z","timestamp":1414454400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["LUTS"],"published-print":{"date-parts":[[2016,5]]},"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>We investigated the relaxant effect of stimulation of prostaglandin <jats:styled-content style=\"fixed-case\">E<jats:sub>2<\/jats:sub><\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">PGE<jats:sub>2<\/jats:sub><\/jats:styled-content>) receptor subtype <jats:styled-content style=\"fixed-case\">EP2<\/jats:styled-content> as well as the involvement of a cyclic <jats:styled-content style=\"fixed-case\">AMP<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">cAMP<\/jats:styled-content>)\u2010dependent pathway related to stimulation of <jats:styled-content style=\"fixed-case\">EP2<\/jats:styled-content> receptors in urethral function in rats by evaluating effects of <jats:styled-content style=\"fixed-case\">PGE<jats:sub>2<\/jats:sub><\/jats:styled-content> and selective <jats:styled-content style=\"fixed-case\">EP2<\/jats:styled-content> receptor agonist <jats:styled-content style=\"fixed-case\">CP<\/jats:styled-content>\u2010533,536.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Effects of <jats:styled-content style=\"fixed-case\">PGE<jats:sub>2<\/jats:sub><\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">CP<\/jats:styled-content>\u2010533,536 on <jats:styled-content style=\"fixed-case\">cAMP<\/jats:styled-content> accumulation were assessed in Chinese hamster ovary (<jats:styled-content style=\"fixed-case\">CHO<\/jats:styled-content>)\u2010<jats:styled-content style=\"fixed-case\">K1<\/jats:styled-content> cells expressing rat <jats:styled-content style=\"fixed-case\">EP2<\/jats:styled-content> or <jats:styled-content style=\"fixed-case\">EP4<\/jats:styled-content> receptors. Relaxant responses to <jats:styled-content style=\"fixed-case\">PGE<jats:sub>2<\/jats:sub><\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">CP<\/jats:styled-content>\u2010533,536 (0.01\u201310 \u00b5mol\/L) in rat urethral tissue pre\u2010contracted with 10 \u00b5mol\/L phenylephrine were evaluated, and <jats:styled-content style=\"fixed-case\">cAMP<\/jats:styled-content> levels in isolated rat urethral tissue treated with these compounds were determined as well. The effects of <jats:styled-content style=\"fixed-case\">PGE<jats:sub>2<\/jats:sub><\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">CP<\/jats:styled-content>\u2010533,536 (0.003\u20130.3 mg\/kg intravenously) on urethral perfusion pressure (<jats:styled-content style=\"fixed-case\">UPP<\/jats:styled-content>) in anesthetized rats were also evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">PGE<jats:sub>2<\/jats:sub><\/jats:styled-content> concentration\u2010dependently increased the accumulation of <jats:styled-content style=\"fixed-case\">cAMP<\/jats:styled-content> in cells expressing rat <jats:styled-content style=\"fixed-case\">EP2<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">EC<jats:sub>50<\/jats:sub><\/jats:styled-content> value = 1.3 nmol\/L) and <jats:styled-content style=\"fixed-case\">EP4<\/jats:styled-content> receptors (<jats:styled-content style=\"fixed-case\">EC<jats:sub>50<\/jats:sub><\/jats:styled-content> value = 17 nmol\/L). While <jats:styled-content style=\"fixed-case\">CP<\/jats:styled-content>\u2010533,536 similarly increased the accumulation of <jats:styled-content style=\"fixed-case\">cAMP<\/jats:styled-content> in cells expressing rat <jats:styled-content style=\"fixed-case\">EP2<\/jats:styled-content> receptors (<jats:styled-content style=\"fixed-case\">EC<jats:sub>50<\/jats:sub><\/jats:styled-content> value = 3.0 nmol\/L), no such effects were noted in cells expressing rat <jats:styled-content style=\"fixed-case\">EP4<\/jats:styled-content> receptors up to 10 \u00b5mol\/L. Both <jats:styled-content style=\"fixed-case\">PGE<jats:sub>2<\/jats:sub><\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">CP<\/jats:styled-content>\u2010533,536 produced relaxation and increased <jats:styled-content style=\"fixed-case\">cAMP<\/jats:styled-content> levels in urethral tissues in a concentration\u2010dependent manner. <jats:styled-content style=\"fixed-case\">PGE<jats:sub>2<\/jats:sub><\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">CP<\/jats:styled-content>\u2010533,536 both dose\u2010dependently decreased <jats:styled-content style=\"fixed-case\">UPP<\/jats:styled-content> in anesthetized rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Taken together, these results suggest that stimulation of <jats:styled-content style=\"fixed-case\">EP2<\/jats:styled-content> receptors induces relaxation likely via activation of <jats:styled-content style=\"fixed-case\">cAMP<\/jats:styled-content>\u2010dependent mechanisms in rat urethral tissue, leading to a reduction of <jats:styled-content style=\"fixed-case\">UPP<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/luts.12077","type":"journal-article","created":{"date-parts":[[2014,10,28]],"date-time":"2014-10-28T16:23:29Z","timestamp":1414513409000},"page":"125-129","source":"Crossref","is-referenced-by-count":12,"title":["Study on Physiological Roles of Stimulation of Prostaglandin <scp>E<sub>2<\/sub><\/scp> Receptor Subtype <scp>EP2<\/scp> in Urethral Function in Rats"],"prefix":"10.1111","volume":"8","author":[{"given":"Ryoko","family":"KURIHARA","sequence":"first","affiliation":[{"name":"Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma Inc.  Tsukuba Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenichiro","family":"ISHIZU","sequence":"additional","affiliation":[{"name":"Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma Inc.  Tsukuba Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hajime","family":"TAKAMATSU","sequence":"additional","affiliation":[{"name":"Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma Inc.  Tsukuba Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taiji","family":"YOSHINO","sequence":"additional","affiliation":[{"name":"Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma Inc.  Tsukuba Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noriyuki","family":"MASUDA","sequence":"additional","affiliation":[{"name":"Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma Inc.  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