A quantitative analysis of mRNA expression of α1 and β-adrenoceptor subtypes and their functional roles in human normal and obstructed bladders

Purpose: We compared the expression level of alpha1-adrenoceptor (AR) subtype mRNA to that of beta-AR subtype mRNA in control and obstructed human bladders, and examined whether alpha1-AR mediated contraction and beta-AR mediated relaxation of human detrusor muscle are altered by bladder outlet obstruction. Materials and Methods: A real-time quantitative reverse transcriptase-polymerase chain reaction based method was used to quantify alpha1 and beta-AR subtype mRNA expression. The contractile response to alpha-AR agonists and the relaxant effect of beta-AR agonists were examined using an isometric contraction technique. Results: The mRNA of alpha1a, alpha1b, alpha1d, beta1 and beta2-AR mRNAs was expressed at low levels, while beta3-AR was the most highly expressed subtype at the mRNA level in control and obstructed bladders. The expression level of alpha1 and beta-AR subtype mRNA was not significantly different between the 2 groups. The mean contractile response to 10(-4) M phenylephrine +/- SEM was only 4.4% +/- 1.4% and 5.2% +/- 1.4% of the 10(-7) M carbachol induced contraction in the control and obstructed groups, respectively. Contractile responses to phenylephrine were not significantly increased in obstructed bladder. Isoproterenol and the beta3-AR selective agonist L755,507 relaxed human detrusor muscle in a concentration dependent manner (10(-9) to 10(-4) M). However, the beta1/beta2-AR agonist dobutamine and the beta2-AR selective agonist clenbuterol did not produce relaxation at a concentration of 10(-9) to 10(-5) M in the 2 groups. Conclusions: These findings indicate that neither up-regulation of alpha1-ARs nor down-regulation of beta-ARs occurs and relaxation mediating beta3-ARs are by far predominant in the human obstructed bladder. Therefore, it is not likely that bladder alpha1-ARs are responsible for detrusor overactivity and storage symptoms in patients with benign prostatic obstruction.