Pharmacological characterization of beta-adrenoceptor subtypes mediating relaxation in porcine isolated ureteral smooth muscle.
OBJECTIVE
We pharmacologically characterized the functional beta-adrenoceptor subtypes mediating porcine ureteral smooth muscle relaxation.


METHODS
The effects of various beta-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 beta2-adrenoceptor agonists tested (salbutamol, procaterol and terbutaline) attenuated the KCl induced contraction. The 2 beta3-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 beta1-adrenoceptor agonist dobutamine had a relaxing effect on the ureter only at high concentrations (over 1 x 10 M). Isoprenaline induced relaxation was antagonized by the beta2-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 beta1-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 1x 10 M CGP 20712A plus 1 x 10 M ICI-118,551 the beta3-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 beta2 and beta3-adrenergic stimulation, as in humans.
Wanajo
Isao
I
Central Research Laboratory, Kissei Pharmaceutical Co. Ltd., Nagano, Japan.
Tomiyama
Yoshitaka
Y
Yamazaki
Yoshinobu
Y
Kojima
Masami
M
Shibata
Nobuo
N
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D002395:Catecholamines / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000502:physiology*; D009130:Muscle, Smooth / Q000502:physiology*; D011189:Potassium Chloride / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D013552:Swine; D013556:Swine, Miniature; D014513:Ureter / Q000378:metabolism / Q000502:physiology*
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D002395:Catecholamines; D011943:Receptors, Adrenergic, beta; D011189:Potassium Chloride