Characterization of β-Adrenoceptor Subtype in Bladder Smooth Muscle in Cynomolgus Monkey

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Abstract
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 > BRL 37344 > dobutamine, salbutamol, procaterol > xamoterol. In the antagonist experiment, bupranolol (beta-antagonist, 10(-6) to 10(-5) M) and SR 58894A (beta3-antagonist, 10(-7) to 10(-5) M) caused a rightward shift of the concentration-relaxation curve for isoprenaline, but CGP-20712A (beta1-antagonist, 10(-9) to 10(-7) M) and ICI-118551 (beta2-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 beta3-subtype.