Functional and molecular biological evidence for a possible β 3 ‐adrenoceptor in the human detrusor muscle

The possible existence of a β 3 ‐adrenergic receptor (β 3 ‐AR) in the human detrusor muscle was investigated by in vitro functional studies and analysis of mRNA expression. 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) noradrenaline (pD 2 6.07±0.12) adrenaline (pD 2 5.88±0.11). Neither dobutamine (β 1 ‐ and β 2 ‐AR agonist) nor procaterol (β 2 ‐AR agonist) produced any significant relaxation at concentrations up to 10 −5   M . BRL37344A, CL316243 and CGP‐12177A (β 3 ‐AR agonists), relaxed the preparations significantly at concentrations higher than 10 −6   M . The pD 2 values for BRL37344A, CL316243 and CGP‐12177A were 6.42±0.25, 5.53±0.09 and 5.74±0.14, respectively. CGP‐20712A (10 −7 –10 −5   M ), a β 1 ‐AR antagonist, did not affect the isoprenaline‐induced relaxation. On the other hand, ICI‐118,551, a β 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 β 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. The β 1 ‐, β 2 ‐ and β 3 ‐AR mRNAs were all positively expressed in detrusor smooth muscle preparations in a reverse transcription polymerase chain reaction assay. In conclusion, the present results provide the first evidence for the existence of the β 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 β 3 ‐AR activation.British Journal of Pharmacology (1999) 126 , 819–825; doi: 10.1038/sj.bjp.0702358