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

The Japanese Journal of Pharmacology

Yasuhiko Igawa¹  Osamu Nishizawa¹  Masuo Akahane²  Yoshinobu Yamazaki²  Hiroo Takeda²  Hiroshi Miyata²  Satoshi Akahane² 

[1] Department of Urology, Shinshu University School of Medicine;Division of Discovery Research, Central Research Laboratory, Kissei Pharmaceutical Co., Ltd.

关键词: β-Adrenoceptor;    β3-Adrenoceptor;    Monkey;    Detrusor;    Bladder;   

DOI  :  10.1254/jjp.88.108

学科分类：药理学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(19)Cited-By(15)We first investigated the relaxations of the urinary bladder induced by β-adrenoceptor agonists in anesthetized cynomolgus monkeys and then employed a variety of β-adrenoceptor agonists and antagonists in vitro to identify the β-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 β-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 (β-antagonist, 10−6 to 10−5 M) and SR 58894A (β3-antagonist, 10−7 to 10−5 M) caused a rightward shift of the concentration-relaxation curve for isoprenaline, but CGP-20712A (β1-antagonist, 10−9 to 10 −7 M) and ICI-118551 (β2-antagonist, 10−9 to 10−7 M) did not. The present functional study provides the first evidence that relaxation of the monkey detrusor by β-adrenoceptor activation is mediated via the β3-subtype.

【 授权许可】

Unknown