{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T02:50:17Z","timestamp":1789786217017,"version":"4.0.1"},"reference-count":44,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2016,6,3]],"date-time":"2016-06-03T00:00:00Z","timestamp":1464912000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["ERC\u20102012\u2010StG\u201020111109"],"award-info":[{"award-number":["ERC\u20102012\u2010StG\u201020111109"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2016,7]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>The aims of the present study were to characterize the role of PAR1 in rat bladder under inflammatory conditions and determine whether a selective PAR1 antagonist, F16357, can prevent the pathophysiological symptoms of cyclophosphamide\u2010induced interstitial cystitis (IC).<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Immunohistochemistry, contractile activity in isolated bladder and urodynamics were determined before and after cyclophosphamide treatment. F16357 was administered intravesically during the acute phase of inflammation, and effects on PAR1 and PAR1\u2010related bladder contraction evaluated 24\u00a0h after cyclophosphamide injection. Urodynamics and associated voided volumes were recorded 7 and 24\u00a0h after cyclophosphamide.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>In control conditions, PAR1 was present only in some umbrella cells. Cyclophosphamide disrupted the urothelium and expression of PAR1 by all remaining urothelial cells. After F16357 treatment, urothelial damage was absent and PAR1 immunoreactivity similar to control tissues. Thrombin and TFLLR\u2010NH<jats:sub>2<\/jats:sub> induced bladder contractions. These were increased in inflammatory conditions and antagonized by F16357 in a concentration\u2010dependent manner. In telemetric experiments, furosemide increased urine production and voiding frequency for 60\u00a0min, 7\u00a0h after cyclophosphamide injection. Intravesical administration of F16357 blocked these changes with a return to a physiological profile; 24\u00a0h after cyclophosphamide, the volume of micturition was still lower with no increase in number of micturitions. F16357 30\u00a0\u03bcM reduced the number of micturitions and improved bladder capacity, but did not affect diuresis. Under similar experimental conditions, lidocaine 2% induced comparable effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>PAR1 is expressed in rat bladder, overactivated in inflammatory conditions and involved in bladder function and sensation. F16357 could represent an interesting candidate for IC treatment.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.13501","type":"journal-article","created":{"date-parts":[[2016,4,25]],"date-time":"2016-04-25T15:17:38Z","timestamp":1461597458000},"page":"2224-2236","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["F16357, a novel protease\u2010activated receptor 1 antagonist, improves urodynamic parameters in a rat model of interstitial cystitis"],"prefix":"10.1111","volume":"173","author":[{"given":"N","family":"Monjotin","sequence":"first","affiliation":[{"name":"Institut de Recherche Pierre Fabre  Castres France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Gillespie","sequence":"additional","affiliation":[{"name":"Newcastle University  Newcastle upon Tyne 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