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alpha 1-ADRENERGIC RECEPTOR SUBTYPES IN HUMAN DETRUSOR

1998; Lippincott Williams & Wilkins; Volume: 160; Issue: 3 Part 1 Linguagem: Inglês

10.1016/s0022-5347(01)62836-2

1527-3792

Brian J. Malloy, David T. Price, Rachel Price, ALAN M. BIENSTOCK, Mark K. Dole, BONNIE L. FUNK, Xiaowen L. Rudner, Charlene D. Richardson, Craig F. Donatucci, Debra A. Schwinn,

Pediatric Urology and Nephrology Studies

No AccessJournal of UrologyInvestigative Urology1 Sep 1998alpha1-ADRENERGIC RECEPTOR SUBTYPES IN HUMAN DETRUSOR BRIAN J. MALLOY, DAVID T. PRICE, R. REYN PRICE, ALAN M. BIENSTOCK, MARK K. DOLE, BONNIE L. FUNK, XIAOWEN L. RUDNER, CHARLENE D. RICHARDSON, CRAIG F. DONATUCCI, and DEBRA A. SCHWINN BRIAN J. MALLOYBRIAN J. MALLOY , DAVID T. PRICEDAVID T. PRICE , R. REYN PRICER. REYN PRICE , ALAN M. BIENSTOCKALAN M. BIENSTOCK , MARK K. DOLEMARK K. DOLE , BONNIE L. FUNKBONNIE L. FUNK , XIAOWEN L. RUDNERXIAOWEN L. RUDNER , CHARLENE D. RICHARDSONCHARLENE D. RICHARDSON , CRAIG F. DONATUCCICRAIG F. DONATUCCI , and DEBRA A. SCHWINNDEBRA A. SCHWINN View All Author Informationhttps://doi.org/10.1016/S0022-5347(01)62836-2AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: To identify and quantitate alpha1-adrenergic receptor (alpha1 AR) subtype expression in human detrusor. Materials and Methods: Initial studies to determine alpha1 AR expression in human detrusor were performed using saturation binding with [(125) I]HEAT. Once the presence of alpha1 ARs was documented, subtype (alpha1a, alpha1b, alpha1d) expression at the mRNA level (and comparison with rat) was determined with RNase protection assays (human detrusor) and RT-PCR (human detrusor, rat whole bladder). Competition binding analysis with the alpha1d AR-selective ligand BMY7378 was used to measure alpha1 AR subtype expression at a protein level in human detrusor. Results: alpha1 AR expression in human detrusor was low but reproducible (6.3 +/- 1.0 fmol./mg. total protein). RNase protection assays performed on total RNA extracted from human detrusor revealed the following alpha1 AR subtype expression: alpha1d (66%) > alpha1a (34%), and no alpha1b. RT-PCR confirmed alpha1 AR subtype mRNA distribution in human detrusor with alpha1d ([nearly =] 60-70%) > alpha (1a) ([nearly =] 30-40%), and a lack of alpha1b mRNA. Rat whole bladder expressed different alpha1 AR subtype mRNA than human detrusor, with alpha1a [nearly =] alpha1b [nearly =] alpha 1d. The presence of alpha1d > alpha1a expression in human detrusor was confirmed at a protein level by competition analysis utilizing BMY7378 which revealed a two-site fit, with Ki and high affinity binding (66%) consistent with the alpha1d AR subtype. Conclusions: Human detrusor contained two alpha1 AR subtypes (alpha (1d) > alpha1a), a finding that is different from rat, another commonly used animal model. Since non-subtype selective alpha1 AR antagonists ameliorate irritative bladder symptoms (in men and women with/without outlet obstruction), and Rec 15/2739 (alpha1a selective antagonist) does not improve symptom scores in BPH, our findings suggest bladder alpha1d ARs may provide a potentially novel mechanism underlying these therapeutic benefits. References 1 : Voiding dysfunction: diagnosis, classification, and management. In: Adult and Pediatric Urology, Third Edition. Edited by . St. Louis: Mosby-Year Book, Inc.1996: 1220. Google Scholar 2 : Voiding function: relevant anatomy, physiology, pharmacology, and molecular aspects. In: Adult and Pediatric Urology, Third Edition.. Edited by . St. Louis: Mosby-Year Book, Inc.1997: 1159. Google Scholar 3 : Detrusor morphology in relation to bladder outflow obstruction and instability. In: Benign Prostatic Hypertrophy.. Edited by . Berlin: Springer-Verlag1997: 666. 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Volume 160Issue 3 Part 1September 1998Page: 937-943 Advertisement Copyright & Permissions© 1998 by American Urological Association, Inc.MetricsAuthor Information BRIAN J. MALLOY More articles by this author DAVID T. PRICE More articles by this author R. REYN PRICE More articles by this author ALAN M. BIENSTOCK More articles by this author MARK K. DOLE More articles by this author BONNIE L. FUNK More articles by this author XIAOWEN L. RUDNER More articles by this author CHARLENE D. RICHARDSON More articles by this author CRAIG F. DONATUCCI More articles by this author DEBRA A. SCHWINN More articles by this author Expand All Advertisement PDF downloadLoading ...