{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T08:17:14Z","timestamp":1788164234537,"version":"build-2803163510"},"reference-count":30,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neurourology and Urodynamics"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>To investigate the adenosine receptor (AR) mechanism underlying bladder outlet obstruction (BOO)\u2010related bladder dysfunction, we examined the expression level of AR subtypes in bladder tissues, and the effects of AR subtypes A2B &amp; A3 modulation on bladder activity using male BOO rats, and Dahl rats with A2B receptor deletion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>BOO was induced by partial ligation of the proximal urethra in male Sprague\u2010Dawley rats. At 4 weeks after BOO, conscious cystometrograms (CMG) were performed with the urethral ligature being intact. The effects of AR A3 agonist (2CL\u2010IB\u2010MECA) and AR A3 antagonist (MRS3777) were examined by intravesical administration. Furthermore, we examined the difference of bladder function of AR subtypes between AR A2B knockout (A2B\u2010KO) and wild\u2010type groups of male Dahl rats. mRNA levels of AR subtypes in bladder tissues were also analyzed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      BOO versus sham rats showed heavier bladder weights, higher contraction amplitudes, and increased numbers of non\u2010voiding contractions (NVCs) during the filling phase. In the bladder mucosa \u2013 but not the detrusor \u2010 of BOO versus sham rats, mRNA expression levels of A2A and A3 AR were significantly increased, while A2B levels were significantly decreased. In BOO rats, an A3 antagonist (MRS 3777; 10 and 100\u2009\u03bcM) had no effect on CMG parameters. However, a high dose of an A3 agonist (2CL\u2010IB\u2010MECA; 100\u2009\u03bcM) significantly increased NVCs (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0034), an effect that was blocked by the A3 antagonist. Additionally, compared to wild\u2010type rats, A2B\u2010KO rats showed a significant increase in the number of NVCs (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0039).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>A2B AR down\u2010regulation in BOO rats and A2B deletion in Dahl rats could contribute to the development of bladder overactivity. Moreover, a high\u2010level of exogenous activation of A3 ARs might exacerbate bladder overactivity in BOO.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/nau.70430","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T07:51:06Z","timestamp":1788162666000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Functional Roles of Adenosine A\n                    <sub>2B<\/sub>\n                    and A\n                    <sub>3<\/sub>\n                    Receptor Subtypes in the Bladder of Male Rats With A\n                    <sub>2B<\/sub>\n                    Receptor Deletion or Bladder Outlet Obstruction"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5819-523X","authenticated-orcid":false,"given":"Masahiro","family":"Kurobe","sequence":"first","affiliation":[{"name":"Department of Urology University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA"},{"name":"Department of Systems Physiology, Graduate School of Medicine University of the Ryukyus Ginowan Okinawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1814-8949","authenticated-orcid":false,"given":"Ei\u2010ichiro","family":"Takaoka","sequence":"additional","affiliation":[{"name":"Department of Urology University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0731-4577","authenticated-orcid":false,"given":"Kanako","family":"Matsuoka","sequence":"additional","affiliation":[{"name":"Department of Urology University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2164-3091","authenticated-orcid":false,"given":"Shingo","family":"Kimura","sequence":"additional","affiliation":[{"name":"Department of Urology University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5063-4293","authenticated-orcid":false,"given":"Anne M.","family":"Robertson","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering and Materials Science University of Pittsburgh Pittsburgh Pennsylvania USA"},{"name":"Department of Bioengineering University of Pittsburgh Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8101-6009","authenticated-orcid":false,"given":"Edwin K.","family":"Jackson","sequence":"additional","affiliation":[{"name":"Department of Pharmacology &amp; Chemical Biology University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3393-2256","authenticated-orcid":false,"given":"Lori A.","family":"Birder","sequence":"additional","affiliation":[{"name":"Department of Pharmacology &amp; Chemical Biology University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA"},{"name":"Department of Medicine University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3669-4510","authenticated-orcid":false,"given":"Minoru","family":"Miyazato","sequence":"additional","affiliation":[{"name":"Department of Systems Physiology, Graduate School of Medicine University of the Ryukyus Ginowan Okinawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8070-1664","authenticated-orcid":false,"given":"Naoki","family":"Yoshimura","sequence":"additional","affiliation":[{"name":"Department of Urology University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA"},{"name":"Department of Pharmacology &amp; Chemical Biology University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,31]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1016\/j.eururo.2006.02.018","article-title":"A Shifted Paradigm for the Further Understanding, Evaluation, and Treatment of Lower Urinary Tract Symptoms in Men: Focus on the Bladder","volume":"49","author":"Chapple C. 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