Characterization of β-adrenoceptor subtype in bladder smooth muscle in cynomolgus monkey

We first investigated the relaxations of the urinary bladder induced by beta-adrenoceptor agonists in anesthetized cynomolgus monkeys and then employed a variety of beta-adrenoceptor agonists and antagonists in vitro to identify the beta-adrenoceptor subtype responsible for the relaxation (using isolated monkey detrusors). Isoprenaline reduced bladder pressure in a dose-dependent manner. Isoprenaline, noradrenaline and adrenaline each produced a concentration-dependent relaxation of isolated detrusor strips, the rank order of relaxing potencies being isoprenaline>noradrenaline>adrenaline. Subtype-selective beta-adrenoceptor agonists also relaxed isolated detrusor strips, the rank order of potencies being CGP-12177>BRL37344>dobutamine, salbutamol, procaterol>xamoterol. In the antagonist experiment, bupranolol (beta-antagonist, 10(-6) to 10(-5) M) and SR 58894A (beta(3)-antagonist, 10(-7) to 10(-5) M) caused a rightward shift of the concentration-relaxation curve for isoprenaline, but CGP-20712A (beta(1)-antagonist. 10(-9) to 10(-7) M) and ICI-118551 (beta(2)-antagonist, 10(-9) to 10(-7) M) did not. The present functional Study provides the first evidence that relaxation of the monkey detrusor by beta-adrenoceptor activation is mediated via the beta(3)-subtype.