PHARMACOLOGICAL CHARACTERIZATION OF β-ADRENOCEPTOR SUBTYPES MEDIATING RELAXATION IN PORCINE ISOLATED URETERAL SMOOTH MUSCLE

ABSTRACT Purpose: We pharmacologically characterized the functional β-adrenoceptor subtypes mediating porcine ureteral smooth muscle relaxation. Materials and Methods: The effects of various β-adrenoceptor agonists and antagonists on KCl induced tonic contractions in isolated porcine ureteral preparations were evaluated using a functional experimental technique. Results: The rank order of potency for the catecholamines tested was isoprenaline > adrenaline > noradrenaline. All β 2 -adrenoceptor agonists tested (salbutamol, procaterol and terbutaline) attenuated the KCl induced contraction. The 2 β 3 -adrenoceptor agonists CL-316243 (( R , R )-5-[2-[[2-(3-chlorophenyl)-2-hydroxyethylamino]propyl]-1,3-benzodioxole-2,2-dicarboxylate], Kissei, Nagano, Japan) and CGP-12177A ((±)[4-[3[(1,1-dimethylethyl)amino]-2-hydroxypropoxy]-1,3-dihydro-2 H -benzimidazol-2-one hydrochloride], Funakoshi, Tokyo, Japan) also relaxed the ureter. The β 1 -adrenoceptor agonist dobutamine had a relaxing effect on the ureter only at high concentrations (over 1 × 10 −5 M). Isoprenaline induced relaxation was antagonized by the β 2 -adrenoceptor antagonist ICI-118,551 ((±)-1-[(2,3-dihydro-7-methyl-1 H -inden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanol hydrochloride, Sigma, St. Louis, Missouri) but not by the β 1 -adrenoceptor antagonist CGP 20712A ((±)-2-hydroxy-5-[2-[[2-hydroxy-3-[4-[1-methyl-4-(trifluoromethyl)-1 H -imidazol-2-yl]phenoxy]propyl]amino]ethoxy]-benzamide methanesulphonate, Funakoshi). In the presence of 1× 10 −7 M CGP 20712A plus 1 × 10 −7 M ICI-118,551 the β 3 -adrenoceptor antagonist SR 58894A (3-(2-allylphenoxy)-1-[(1 S )-1,2,3,4-tetrahydronaphth-1-ylamino]-(2 S )-2-propanol hydrochloride, Kissei) antagonized isoprenaline induced relaxation. Conclusions: Our results suggest that porcine ureteral smooth muscle is relaxed by β 2 and β 3 -adrenergic stimulation, as in humans.