Characterization of beta 3-adrenoceptor-mediated relaxation in rat abdominal aorta smooth muscle.
The present study was carried out to characterize beta-adrenoceptor subtypes mediating relaxation of rat abdominal aorta smooth muscle. (-)-Isoprenaline and a nonconventional beta(3)-adrenoceptor agonist, (+/-)-[4-[3-[(1,1-dimethylethyl)amino]-2-hydroxypropoxy]-1,3-dihydro-2H-benzimida zol-2-one] hydrochloride ((+/-)-CGP12177A), induced concentration-dependent relaxation of (-)-phenylephrine (0.3 microM) preconstricted spiral preparations. Pretreatment with a combination of (+/-)-2-hydroxy-5-[2-[[2-hydroxy-3-[4-[1-methyl-4-(trifluoromethyl)-1H-imidazol-2 -yl]phenoxy]propyl]amino]ethoxy]-benzamide methanesulfonate (CGP20712A, a selective beta(1)-adrenoceptor antagonist) and (+/-)-1-[2,3-(dihydro-7-methyl-1H-inden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-buta nol hydrochloride (ICI-118,5511, a selective beta(2)-adrenoceptor antagonist) (0.1 microM for each) produced a 14-fold rightward shift of the concentration-response curve for (-)-isoprenaline; however, the relaxation in response to (+/-)-CGP12177A was unaffected by the blockade of beta(1)- and beta(2)-adrenoceptors. In the presence of CGP20712A and ICI-118,551 (0.1 microM for each), the concentration-response curves for (-)-isoprenaline and (+/-)-CGP12177A were shifted to the right by a nonselective beta(1)-, beta(2)- and beta(3)-adrenoceptor antagonist, (+/-)-bupranolol (3 and 10 microM). These results clearly suggest that beta(3)-adrenoceptors are involved in beta-adrenoceptor-mediated relaxation of rat abdominal aorta smooth muscle.
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CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL GENE-N GENE-N GENE-Y GENE-N CHEMICAL GENE-Y GENE-N GENE-Y GENE-Y GENE-Y CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL
(+/-)-2-hydroxy-5-[2-[[2-hydroxy-3-[4-[1-methyl-4-(trifluoromethyl)-1H-imidazol-2 -yl]phenoxy]propyl]amino]ethoxy]-benzamide methanesulfonate CGP20712A (+/-)-1-[2,3-(dihydro-7-methyl-1H-inden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-buta nol hydrochloride ICI-118,5511 (-)-isoprenaline (+/-)-CGP12177A beta(1)- and beta(2)-adrenoceptors beta(1)-, beta(2)- and beta(3)-adrenoceptor beta(3)-adrenoceptors beta-adrenoceptor CGP20712A beta(3)-adrenoceptor beta-adrenoceptor beta(1)-adrenoceptor beta(2)-adrenoceptor beta 3-adrenoceptor ICI-118,551 (-)-isoprenaline (+/-)-CGP12177A (+/-)-bupranolol (-)-Isoprenaline (+/-)-[4-[3-[(1,1-dimethylethyl)amino]-2-hydroxypropoxy]-1,3-dihydro-2H-benzimida zol-2-one] hydrochloride (+/-)-CGP12177A (-)-phenylephrine