title: Characterization of beta-adrenoceptor subtype in bladder smooth muscle in cynomolgus monkey.
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.
authors.affiliation: Division of Discovery Research, Central Research Laboratory, Kissei Pharmaceutical Co., Ltd., Nagano, Japan. hiroo_takeda@pharm.kissei.co.jp
authors.forename: Hiroo
authors.initials: H
authors.lastname: Takeda
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Yamazaki
authors.forename: Masuo
authors.initials: M
authors.lastname: Akahane
authors.forename: Satoshi
authors.initials: S
authors.lastname: Akahane
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Miyata
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Igawa
authors.forename: Osamu
authors.initials: O
authors.lastname: Nishizawa
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D005260:Female; D007545:Isoproterenol / Q000494:pharmacology; D008252:Macaca fascicularis / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D011312:Pressure; D011943:Receptors, Adrenergic, beta / Q000145:classification* / Q000378:metabolism*; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; D007545:Isoproterenol