Characterization of beta-adrenoceptor subtypes in the ferret urinary bladder in vitro and in vivo

In the present study, the beta-adrenoceptor subtypes distributed in the det rusor of the ferret were investigated in functional experiments in vitro an d in vivo using a variety of beta-adrenoceptor agonists and antagonists. Al l the beta-adrenoceptor agonists tested relaxed the isolated detrusor strip , the rank order of potency being (+/-)-(R*,R*)-[4-[2-[[2-(3-chlorophenyl)- 2-hydroxyethyl]-amino]propyl]phenoxy]-acetic acid sodium (BRL 37344A) > (+/ -)-4-(3-t-butylamino-2-hydroxypropoxy) benzimidazol-2-one (CGP-12177A), iso prenaline and (R,R)-5-[2-[[2-(3-chlorophenyl)-2-hydroxyethylamino]propyl]-1 ,3-benzodioxole-2,2-dicarboxylate (CL 316,243) > dobutamine and procaterol. In antagonist experiment, 3-(2-allylphenoxy)-1-[(1S)-1,2,3,4-tetrahydro-na phth-1-ylamino]-(2S)-2-propanol hydrochloride (SR 58894A), but neither 2-hy droxy-5(2-((2-hydroxy-3-(4-((1-methyl-4-trifluoromethyl)1H-imidazole-2-yl)- phenoxy)propyl)amino)ethoxy)-benzamide monomethane sulphonate (CGP-20712A) nor erythro-(+/-)-1-(7-methylindan-4-yloxy)-3-isopropylaminobutan-2-ol hydr ochloride (ICI-118,551), caused a rightward shift of the concentration-rela xation curve for isoprenaline. In in vivo experiments, isoprenaline and CL 316,243 each reduced bladder pressure in a dose-dependent manner. CL 316,24 3 was the only drug that did not produce any significant influences on bloo d pressure and heart rate at doses that reduced bladder pressure. The prese nt functional study provides the first evidence that relaxation of the ferr et detrusor by beta-adrenoceptor activation is mediated mainly via the beta (3)-adrenoceptor, as in the human detrusor. (C) 2000 Elsevier Science B.V. All rights reserved.