{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T11:57:56Z","timestamp":1784030276405,"version":"3.55.0"},"reference-count":28,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2013,10,2]],"date-time":"2013-10-02T00:00:00Z","timestamp":1380672000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2013,12]]},"abstract":"<jats:title>New findings<\/jats:title><jats:p><jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p><jats:bold>What is the central question of this study?<\/jats:bold><\/jats:p><jats:p>Given that the bladder in 60% of patients with detrusor overactivity exhibits increased atropine\u2010resistant contractile responses to nerve stimulation and that high intravesicular pressure is associated with episodes of hypoxia\u2013glucopenia and reperfusion, we asked whether cycles of hypoxia\u2013glucopenia and reoxygenation increases purinergic signalling in the rat bladder <jats:italic>in vitro<\/jats:italic>.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p><jats:bold>What is the main finding and its importance?<\/jats:bold><\/jats:p><jats:p>Four cycles of hypoxia\u2013glucopenia and reoxygenation augmented atropine\u2010resistant contractile responses of rat detrusor muscle strips subjected to electrical field stimulation via increased purinoceptor P2X<jats:sub>1<\/jats:sub> expression and ATP release. Purinergic antagonists blocked this augmentation, suggesting a possible therapeutic role for purinergic antagonists in the treatment of detrusor overactivity.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><jats:p>Bladders from patients with detrusor overactivity have an increased atropine\u2010resistant contractile response to nerve stimulation. The bladder has also been shown to be very susceptible to hypoxia\u2013glucopenia and reperfusion injury, leading to the hypothesis that episodes of hypoxia\u2013glucopenia and reoxygenation result in increased atropine\u2010resistant responses to nerve stimulation in the detrusor muscle. Detrusor muscle strips were suspended in a Perspex organ bath chamber of volume 0.2 ml perfused with Krebs solution at 37\u00b0C aerated with 21% O<jats:sub>2<\/jats:sub>, 5% CO<jats:sub>2<\/jats:sub> and the balance nitrogen. Hypoxia\u2013glucopenia was induced by switching perfusion to Krebs solution without glucose, gassed with 95% nitrogen and 5% CO<jats:sub>2<\/jats:sub>. Atropine\u2010resistant contractile responses increased by 40.5 \u00b1 7.3% after four cycles of hypoxia\u2013glucopenia (10 min) and reoxygenation (1 h), whereas \u03b1,\u03b2\u2010methylene ATP\u2010resistant responses did not increase. Expression of P2X<jats:sub>1<\/jats:sub> receptors in the bladder was increased after hypoxia\u2013glucopenia and reoxygenation cycling, and ATP release from stimulated bladder strips during cycling was also increased. Other P2X receptor\u2010mediated mechanisms may also be involved in the augmentation of bladder contraction during hypoxia\u2013glucopenia and reoxygenation cycling, because a non\u2010specific P2X antagonist blocked most of the augmented response, whereas a P2X<jats:sub>1<\/jats:sub>\u2010specific antagonist prevented only part of the augmentation of contractile response induced by hypoxia\u2013glucopenia and reoxygenation. In conclusion, four cycles of hypoxia\u2013glucopenia and reoxygenation increased the purinergic, but not the cholinergic, contractile responses to nerve stimulation. Increased P2X<jats:sub>1<\/jats:sub> receptor expression and ATP release may have contributed to the augmentation of contractile response induced by hypoxia\u2013glucopenia and reoxygenation. Purinergic antagonists may, therefore, be a useful therapeutic option for the treatment of overactive bladder with increased purinergic\u2010mediated contractions.<\/jats:p>","DOI":"10.1113\/expphysiol.2013.075010","type":"journal-article","created":{"date-parts":[[2013,8,24]],"date-time":"2013-08-24T02:32:31Z","timestamp":1377311551000},"page":"1683-1695","source":"Crossref","is-referenced-by-count":7,"title":["Enhanced purinergic contractile responses and P2X<sub>1<\/sub> receptor expression in detrusor muscle during cycles of hypoxia\u2013glucopenia and reoxygenation"],"prefix":"10.1113","volume":"98","author":[{"given":"R. A.","family":"Elliott","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Tonnu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Ghaffar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. H.","family":"Taylor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. G.","family":"Tincello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. I.","family":"Norman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,10,2]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/nau.10052"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(05)68236-5"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(05)68247-X"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/003655999750042114"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1080\/03008880410015336"},{"key":"e_1_2_5_7_1","first-page":"255","article-title":"Hypoxia as an etiological factor in bladder instability: implications for therapy","volume":"539","author":"Brading AF","year":"2003","journal-title":"Adv Exp Med Biol"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1990.tb12956.x"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1159\/000028323"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(17)45194-9"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0094-0143(05)70288-3"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(05)64632-0"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3115-06.2007"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(05)64843-4"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ju.0000131244.67160.f4ABSTRACT"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0883-9441(99)90020-5"},{"key":"e_1_2_5_17_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1523\/JNEUROSCI.21-18-j0002.2001","article-title":"Loss of purinergic P2X3 and P2X5 receptor innervation in human detrusor from adults with urge incontinence","volume":"21","author":"Moore KH","year":"2001","journal-title":"J Neurosci"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-1241.2008.01737.x"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0531-5565(02)00094-3"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(05)65403-1"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(01)64784-0"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-410X.2008.07587.x"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(17)53509-0"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2005.04.021"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0703720"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI24086"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2009.01.007"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(05)68248-1"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0531-5565(00)00175-3"}],"container-title":["Experimental Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1113%2Fexpphysiol.2013.075010","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/expphysiol.2013.075010","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T05:38:36Z","timestamp":1697607516000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/expphysiol.2013.075010"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,10,2]]},"references-count":28,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2013,12]]}},"alternative-id":["10.1113\/expphysiol.2013.075010"],"URL":"https:\/\/doi.org\/10.1113\/expphysiol.2013.075010","archive":["Portico"],"relation":{},"ISSN":["0958-0670","1469-445X"],"issn-type":[{"value":"0958-0670","type":"print"},{"value":"1469-445X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,10,2]]}}}