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• W2040249269 abstract "No AccessJournal of UrologyINVESTIGATIVE UROLOGY1 Dec 2003The Functional Role of β-Adrenoceptor Subtypes in Mediating Relaxation of Pig Urethral Smooth Muscle TOMONORI YAMANISHI, CHRISTOPHER R. CHAPPLE, KOSAKU YASUDA, KEN-ICHIRO YOSHIDA, and RUSSELL CHESS-WILLIAMS TOMONORI YAMANISHITOMONORI YAMANISHI More articles by this author , CHRISTOPHER R. CHAPPLECHRISTOPHER R. CHAPPLE More articles by this author , KOSAKU YASUDAKOSAKU YASUDA More articles by this author , KEN-ICHIRO YOSHIDAKEN-ICHIRO YOSHIDA More articles by this author , and RUSSELL CHESS-WILLIAMSRUSSELL CHESS-WILLIAMS More articles by this author View All Author Informationhttps://doi.org/10.1097/01.ju.0000085596.11247.78AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: The predominant β-adrenoceptor subtype present in the bladder and urethra is β3-adrenoceptors. We investigated the role of β-adrenoceptors in mediating relaxation of the in vitro female pig urethra. Materials and Methods: Circular strips of urethral tissues were pre-contracted with KCl. Concentration-relaxation curves (CRCs) to β-adrenoceptor agonists were obtained in the absence and presence of antagonists. Results: The nonselective β-agonist isoproterenol in 30 animals and the β3-adrenoceptor agonist BRL37344 in 4 relaxed with high potency (pEC50 7.2 and 8.1, respectively), while the β2-adrenoceptor agonist salbutamol in 6 had low potency (pEC50 6.1). Mean maximal relaxation responses of BRL37344 and salbutamol relative to maximal isoproterenol responses were 89.8% and 76.7%, respectively. Propranolol (10 to 100 nM) in 18 animals antagonized CRCs to isoproterenol with high affinity (apparent pKB 8.6) but the Schild plot had a slope that was significantly less than unity (0.68, p <0.01). High concentrations of the β1-antagonist CGP20712A (3 to 30 μM) in 12 animals had no effect on responses to isoproterenol. The β2-antagonist ICI118551 (30 to 300 nM) in 25 animals antagonized responses to isoproterenol with high affinity (apparent pKB 8.03) with a Schild slope not different from unity (0.79). The β3-antagonist SR59230A (10 to 100 nM) in 12 animals antagonized CRCs to isoproterenol with an apparent pKB of 7 and with a Schild slope that was again significantly less than unity (0.62, p <0.01), indicating that responses to isoproterenol are mediated by more than 1 β-adrenoceptor subtype. According to the Schild plot of unity ICI118551 (3 to 30 nM) in 18 animals competitively antagonized responses to salbutamol with high affinity (pA2 8.5). Conclusions: In the pig urethra β-adrenoceptor mediated relaxations to isoproterenol are mediated via β2 and β3-adrenoceptors, while responses to β2-adrenoceptor agonists such as salbutamol appear to be mediated only via β2-adrenoceptors. References 1 : Function and distribution of beta 3-adrenoceptors in rat, rabbit and human urinary bladder and external urethral sphincter. J Smooth Muscle Res2000; 36: 21. Google Scholar 2 : Inhibition of the contractile responses of isolated human and rat bladders by clenbuterol. J Urol2001; 166: 1969. Abstract, Google Scholar 3 : The role of beta(3)-adrenoceptors in mediating relaxation of porcine detrusor muscle. Br J Pharmacol2002; 135: 129. Google Scholar 4 : Effects of selective β2 and β3-adrenoceptor agonists on detrusor hyperreflexia in conscious cerebral infracted rats. J Urol2002; 168: 1247. 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Br J Pharmacol1998; 123: 1517. Google Scholar 12 : Involvement of accumulated endogenous NOS inhibitors and decreased NOS activity in the impaired neurogenic relaxation of the rabbit proximal urethra with ischaemia. Br J Pharmacol2001; 133: 97. Google Scholar 13 : The role of M2 muscarinic receptor subtypes in mediating contraction of the pig bladder base after cyclic adenosine monophosphate elevation and/or selective M3 inactivation. J Urol2002; 167: 397. Link, Google Scholar 14 : The role of M2-muscarinic receptor subtypes mediating contraction of the circular and longitudinal smooth muscle of the pig proximal urethra. J Urol2002; 168: 308. Abstract, Google Scholar 15 : Identification of β-adrenoceptor subtypes in lower urinary tract of the female pig. J Urol2002; 168: 2706. Abstract, Google Scholar 16 : Role of beta-adrenoceptor subtypes in mediating relaxation of the pig bladder trigonal muscle in vitro. Neurourol Urodyn2003; 22: 338. Google Scholar 17 : Morphological aspects of the female pig bladder neck and urethra: quantitative analysis using computer assisted 3-dimensional reconstructions. J Urol2001; 165: 1294. Link, Google Scholar 18 : Functional identification of rat atypical beta-adrenoceptors by the first beta 3-selective antagonists, aryloxypropanolaminotetralins. Br J Pharmacol1996; 117: 435. Google Scholar 19 : Pharmacological characterization of beta-adrenoceptors mediating relaxation of the rat urinary bladder in vitro. Br J Pharmacol1999; 127: 1744. Google Scholar 20 : The influence of beta-adrenoceptor and muscarinic receptor agonists and antagonists on the static urethral closure function in healthy females. Scand J Urol Nephrol1993; 27: 31. Google Scholar 21 : Effects of beta2-stimulants on contractility and fatigue of canine urethral sphincter. J Urol1994; 151: 1066. Abstract, Google Scholar From the Department of Urology, Dokkyo University (TY, KY, K-IY), Japan, and Department of Urology, Royal Hallamshire Hospital (CRC) and Department of Biomedical Science, University of Sheffield (RC-W), Sheffield, United Kingdom© 2003 by American Urological Association, Inc.FiguresReferencesRelatedDetails Volume 170Issue 6December 2003Page: 2508-2511 Advertisement Copyright & Permissions© 2003 by American Urological Association, Inc.Keywordsurethraswinemuscle relaxationreceptors, adrenergicmuscle, smoothMetricsAuthor Information TOMONORI YAMANISHI More articles by this author CHRISTOPHER R. CHAPPLE More articles by this author KOSAKU YASUDA More articles by this author KEN-ICHIRO YOSHIDA More articles by this author RUSSELL CHESS-WILLIAMS More articles by this author Expand All Advertisement PDF DownloadLoading ..." @default.
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• W2040249269 title "The Functional Role of β-Adrenoceptor Subtypes in Mediating Relaxation of Pig Urethral Smooth Muscle" @default.
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