British Journal of Pharmacology 2004-06-01

ALpha1-adrenoceptor antagonist properties of CGP 12177A and other beta-adrenoceptor ligands: evidence against beta(3)- or atypical beta-adrenoceptors in rat aorta.

Nataraj Brahmadevara, Angus M Shaw, Allan MacDonald

Index: Br. J. Pharmacol. 142 , 781-787, (2004)

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Abstract

1. The alpha(1)-adrenoceptor antagonist properties of the beta-adrenoceptor nonconventional partial agonist, CGP 12177A, was investigated in functional assays in rat aorta and in radioligand binding assays in rat cerebral cortical membranes. In addition, binding affinities of other beta-adrenoceptor ligands were measured to investigate any correlation between alpha(1)-adrenoceptor affinity and relaxant potency in phenylephrine-constricted rings. 2. In functional studies, CGP 12177A produced parallel rightward shifts of the phenylephrine CRC with no reduction in the maximum responses. Schild regression analysis gave a straight line with a slope of 0.95 (95% CL: 0.87-1.04), suggesting reversible competitive antagonism, and gave a pK(B) value of 5.26. In contrast, CGP 12177A (