The β3 -adrenoceptor mediates the inhibitory effects of β-adrenoceptor agonists via the urothelium in pig bladder dome

Aims: Relaxation of detrusor muscle via beta-adrenoceptors may contribute to urine storage during bladder filling. Thus there is increasing interest in beta-adrenoceptor agonists as a potential treatment for detrusor overactivity. The role of the urothelium in bladder responses to beta-adrenoceptor agonists is not yet clear, although we have shown that these agonists have a greater inhibitory effect on detrusor contraction when the urothelium is intact. The aim was to determine which beta-adrenoceptor subtype is involved in this effect. Methods: Paired strips of pig bladder dome mucosa-intact and mucosa-denuded, were mounted in tissue baths. Relaxation responses were obtained to beta-adrenoceptor agonists (isoprenaline, dobutamine, salbutamol or BRL37344) in carbachol pre-contracted tissues. Inhibitory effects were studied by obtaining concentration-response curves (CRCs) to carbachol in the presence and absence of beta-adrenoceptor agonists. The inhibitory effects of isoprenaline were also studied following incubation with beta-adrenoceptor antagonists (propranolol, CGP20712, ICI-118, 551 or SR 59230A; non selected, beta(1), beta(2) and beta(3) selective respectively). Results: isoprenaline, dobutamine, salbutamol and BRL37344 all relaxed carbachol pre-contracted tissues and responses were similar in intact and denuded strips. In inhibition experiments, padrenoceptor agonists caused rightward shifts of carbachol CRCs. In intact strips the shift was greater with isoprenaline and BRL37344, but not with dobutamine or salbutamol. This increased shift was still observed in tissues pre-incubated with propranolo, CGP20712 and ICI-118, 551, but not with SR 59230A. Conclusions: beta(3)-adrenoceptors are involved in mediating inhibitory effects of beta-adrenoceptor agonists on detrusor contractions via the urothelium in pig bladder dome.