Beta-adrenoceptor subtypes in the ureteral smooth muscle of rats, rabbits and dogs.
We investigated the beta-adrenoceptor subtypes mediating ureteral relaxation in rats, rabbits and dogs. The relaxing effects of beta-adrenoceptor agonists were evaluated on KCl-induced ureteral contractions. The rank order of potency of the catecholamines tested was isoprenaline > noradrenaline > adrenaline in rat ureter; isoprenaline > adrenaline > noradrenaline in rabbit ureter; only isoprenaline was effective in canine tissues. The beta1-adrenoceptor agonist, dobutamine, produced relaxation of rat ureter. The beta2-adrenoceptor agonist, procaterol, produced more significant relaxation of rabbit ureter than did dobutamine. CL-316243 [(R,R)-5-[2-[[2-(3-chlorophenyl)-2-hydroxyethylamino]propyl]-1,3-b enzodioxole-2,2-dicarboxylate] and CGP-12177A [(+/-)[4-[3[(1,1-dimethylethyl)amino]-2-hydroxypropoxy]-1,3-dihydro-2H-+ ++benzimidazol-2-one hydrochloride], beta3-adrenoceptor agonists, were more effective in relaxing canine ureter than were dobutamine and procaterol. Isoprenaline-induced relaxation was antagonized by a beta1-adrenoceptor antagonist, CGP-20712A [2-hydroxy-5(2-((2-hydroxy-3-(4-((1-methyl-4-trifluoromethyl)1H-imidazol e-2-yl)phenoxy)propyl)amino)ethoxy)-benzamide monomethane sulphonate], in rats and by a beta2-adrenoceptor antagonist, ICI-118,551 [(+/-)-1-[(2,3-dihydro-7-methyl- 1H-inden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanol hydrochloride], in rabbits. The non-selective beta-adrenoceptor antagonist, bupranolol, antagonized isoprenaline-induced relaxation in all species tested. In conclusion, beta-adrenoceptor agonists may relax ureter by stimulating mainly beta1-adrenoceptors in rats, beta2-adrenoceptors in rabbits and mainly beta3-adrenoceptors in dogs.
Division of Discovery Research, Kissei Pharmaceutical, Hotaka, Nagano, Japan.
Y
Y
Tomiyama
K
K
Hayakawa
K
K
Shinagawa
M
M
Akahane
Y
Y
Ajisawa
Y C
YC
Park
T
T
Kurita
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002395:Catecholamines / Q000494:pharmacology; D004285:Dogs; D005260:Female; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000378:metabolism* / Q000502:physiology; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000145:classification* / Q000187:drug effects / Q000378:metabolism; D014513:Ureter / Q000378:metabolism* / Q000502:physiology
D000318:Adrenergic beta-Agonists; D002395:Catecholamines; D011943:Receptors, Adrenergic, beta