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

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Abstract
The possible existence of a β3‐adrenergic receptor (β3‐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 (pD2 6.37±0.07) noradrenaline (pD2 6.07±0.12) adrenaline (pD2 5.88±0.11). Neither dobutamine (β1‐ and β2‐AR agonist) nor procaterol (β2‐AR agonist) produced any significant relaxation at concentrations up to 10−5 M. BRL37344A, CL316243 and CGP‐12177A (β3‐AR agonists), relaxed the preparations significantly at concentrations higher than 10−6 M. The pD2 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 β1‐AR antagonist, did not affect the isoprenaline‐induced relaxation. On the other hand, ICI‐118,551, a β2‐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 pKB value was 5.71±0.19. Moreover, SR58894A (10−7–10−5 M), a β3‐AR antagonist, caused a rightward shift of the concentration‐relaxation curve for isoprenaline in a concentration‐dependent manner. The pA2 value and slope obtained from Schild plots were 6.24±0.20 and 0.68±0.31. The β1‐, β2‐ and β3‐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 β3‐AR subtype in the human detrusor. They also suggest that the relaxation induced by adrenergic stimulation of the human detrusor is mediated mainly through β3‐AR activation. British Journal of Pharmacology (1999) 126, 819–825; doi:10.1038/sj.bjp.0702358