{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:23:03Z","timestamp":1790036583804,"version":"4.0.1"},"reference-count":64,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2016,1,15]],"date-time":"2016-01-15T00:00:00Z","timestamp":1452816000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2016,2]]},"abstract":"<jats:sec>\n                    <jats:title>Linked Article<\/jats:title>\n                    <jats:p>\n                      This article is commented on by Michel, M. C., pp. 429\u2010430 of this issue. To view this commentary visit\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/dx.doi.org\/10.1111\/bph.13379\">http:\/\/dx.doi.org\/10.1111\/bph.13379<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>\n                      Mirabegron is the first \u03b2\n                      <jats:sub>3<\/jats:sub>\n                      \u2010adrenoceptor agonist approved for treatment of overactive bladder syndrome. This study aimed to investigate the effects of \u03b2\n                      <jats:sub>3<\/jats:sub>\n                      \u2010adrenoceptor agonist mirabegron in mouse urethra. The possibility that mirabegron also exerts \u03b1\n                      <jats:sub>1<\/jats:sub>\n                      \u2010adrenoceptor antagonism was also tested in rat smooth muscle preparations presenting \u03b1\n                      <jats:sub>1A<\/jats:sub>\n                      \u2010 (vas deferens and prostate), \u03b1\n                      <jats:sub>1D<\/jats:sub>\n                      \u2010 (aorta) and \u03b1\n                      <jats:sub>1B<\/jats:sub>\n                      \u2010adrenoceptors (spleen).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>\n                      Functional assays were carried out in mouse and rat isolated tissues. Competition assays for the specific binding of [\n                      <jats:sup>3<\/jats:sup>\n                      H]prazosin to membrane preparations of HEK\u2010293 cells expressing each of the human \u03b1\n                      <jats:sub>1<\/jats:sub>\n                      \u2010adrenoceptors, as well as \u03b2\u2010adrenoceptor mRNA expression and cyclic AMP measurements in mouse urethra, were performed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      Mirabegron produced concentration\u2010dependent urethral relaxations that were shifted to the right by the selective \u03b2\n                      <jats:sub>3<\/jats:sub>\n                      \u2010adrenoceptor antagonist L\u2010748,337 but unaffected by \u03b2\n                      <jats:sub>1<\/jats:sub>\n                      \u2010 and \u03b2\n                      <jats:sub>2<\/jats:sub>\n                      \u2010adrenoceptor antagonists (atenolol and ICI\u2010118,551 respectively). Mirabegron\u2010induced relaxations were enhanced by the PDE4 inhibitor rolipram, and the agonist stimulated cAMP synthesis. Mirabegron also produced rightward shifts in urethral contractions induced by the \u03b1\n                      <jats:sub>1<\/jats:sub>\n                      \u2010adrenoceptor agonist phenylephrine. Schild regression analysis revealed that mirabegron behaves as a competitive antagonist of \u03b1\n                      <jats:sub>1<\/jats:sub>\n                      \u2010adrenoceptors in urethra, vas deferens and prostate (\u03b1\n                      <jats:sub>1A<\/jats:sub>\n                      \u2010adrenoceptor, pA\n                      <jats:sub>2<\/jats:sub>\n                      \u00a0\u2245\u00a05.6) and aorta (\u03b1\n                      <jats:sub>1D<\/jats:sub>\n                      \u2010adrenoceptor, pA\n                      <jats:sub>2<\/jats:sub>\n                      \u00a0\u2245\u00a05.4) but not in spleen (\u03b1\n                      <jats:sub>1B<\/jats:sub>\n                      \u2010adrenoceptor). The affinities estimated for mirabegron in functional assays were consistent with those estimated in radioligand binding with human recombinant \u03b1\n                      <jats:sub>1A<\/jats:sub>\n                      \u2010 and \u03b1\n                      <jats:sub>1D<\/jats:sub>\n                      \u2010adrenoceptors (p\n                      <jats:italic>K<\/jats:italic>\n                      <jats:sub>i<\/jats:sub>\n                      \u00a0\u2245\u00a06.0).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Implications<\/jats:title>\n                    <jats:p>\n                      The effects of mirabegron in urethral smooth muscle are the result of \u03b2\n                      <jats:sub>3<\/jats:sub>\n                      \u2010adrenoceptor agonism together with \u03b1\n                      <jats:sub>1A<\/jats:sub>\n                      and \u03b1\n                      <jats:sub>1D<\/jats:sub>\n                      \u2010adrenoceptor antagonism.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.13367","type":"journal-article","created":{"date-parts":[[2015,10,23]],"date-time":"2015-10-23T03:32:50Z","timestamp":1445571170000},"page":"415-428","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":78,"title":["Mirabegron relaxes urethral smooth muscle by a dual mechanism involving \u03b2\n                    <sub>3<\/sub>\n                    \u2010adrenoceptor activation and \u03b1\n                    <sub>1<\/sub>\n                    \u2010adrenoceptor blockade"],"prefix":"10.1111","volume":"173","author":[{"given":"E C","family":"Alexandre","sequence":"first","affiliation":[{"name":"Department of Pharmacology University of Campinas (UNICAMP) Campinas Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L 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