Characterization of beta-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 > 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.
Takeda
Hiroo
H
Division of Discovery Research, Central Research Laboratory, Kissei Pharmaceutical Co., Ltd., Nagano, Japan. hiroo_takeda@pharm.kissei.co.jp
Yamazaki
Yoshinobu
Y
Akahane
Masuo
M
Akahane
Satoshi
S
Miyata
Hiroshi
H
Igawa
Yasuhiko
Y
Nishizawa
Osamu
O
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*
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; D007545:Isoproterenol