Functional and molecular biological evidence for a possible β3-adrenoceptor in the human detrusor muscle

1 The possible existence of a beta(3)-adrenergic receptor (beta(3)-AR) in the human detrusor muscle was investigated by in vitro functional studies and analysis of mRNA expression. 2 Isoprenaline, noradrenaline and adrenaline each produced a concentration-dependent relaxation of the human detrusor. The rank order for their relaxing potencies was isoprenaline (pD(2) 6.37 +/- 0.07) greater than or equal to noradrenaline (pD(2) 6.07 +/- 0.12) greater than or equal to adrenaline (pD(2) 5.88 +/- 0.11). 3 Neither dobutamine (beta(1)- and beta(2)-AR agonist) nor procaterol (beta(2)-AR agonist) produced any significant relaxation at concentrations up to 10(-5) M. BRL37344A, CL316243 and CGP-12177A (beta(3)-AR agonists), relaxed the preparations significantly at concentrations higher than 10(-6) M. The pot values for BRL37344A, CL316243 and CGP-12177A were 6.42 +/- 0.25, 5.53 +/- 0.09 and 5.74 +/- 0.14, respectively. 4 CGP-20712A (10(-7)-10(-5) M), a beta(1)-AR antagonist, did not affect the isoprenaline-induced relaxation. On the other hand, ICI-118,551, a beta(2)-AR antagonist, produced a rightward parallel shift of the concentration-relaxation curve for isoprenaline only at the highest concentration used (10(-5) M) and its pK(B) value was 5.71 +/- 0.19. Moreover, SR58894A (10(-7)-10(-5) M), a beta(3)-AR antagonist, caused a rightward shift of the concentration-relaxation curve for isoprenaline in a concentration-dependent manner. The pA(2) value and slope obtained from Schild plots were 6.24 +/- 0.20 and 0.68 +/- 0.31. 5 The beta(1)-, beta(2)- and beta(3)-AR mRNAs were all positively expressed in detrusor smooth muscle preparations in a reverse transcription polymerase chain reaction assay. 6 In conclusion, the present results provide the first evidence for the existence of the beta(3)-AR subtype in the human detrusor. They also suggest that the relaxation induced by adrenergic stimulation of the human detrusor is mediated mainly through beta(3)-AR activation.