| Autor: |
MALLOY, BRIAN J., PRICE, DAVID T., PRICE, R. REYN, BIENSTOCK, ALAN M., DOLE, MARK K., FUNK, BONNIE L., RUDNER, XIAOWEN L., RICHARDSON, CHARLENE D., DONATUCCI, CRAIG F., SCHWINN, DEBRA A. |
| Zdroj: |
The Journal of Urology; September 1998, Vol. 160 Issue: 3 p937-943, 7p |
| Abstrakt: |
PurposeTo identify and quantitate alpha1-adrenergic receptor (alpha1 AR) subtype expression in human detrusor.Materials and MethodsInitial 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.Resultsalpha1 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.ConclusionsHuman 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. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
|
