Biological Activity
cgp 20712 dihydrochloride is a potent and selective antagonist of β1-adrenoceptor with ic50 value of 0.7 nm [1].β1-adrenoceptor is a g-protein coupled receptor and mediates uncoupling protein-1 (ucp1) gene expression induced by norepinephrine (ne) [2].cgp 20712 dihydrochloride is a potent and selective β1-adrenoceptor antagonist. in neocortical membranes, cgp 20712 a exhibited affinity for β1-adrenoceptor and β2-adrenoceptor with ic50 values of 0.7 and 6700 nm, respectively [1]. in brown adipocytes, cgp-20712a significantly inhibited ucp1 gene expression induced by ne. however, cgp-20712a had no effect on lipolysis. these results suggested that β1-adrenoceptor mediated ucp1 gene expression [2]. in ventricular membranes from rats, cgp 20712a (300 nm) completely occupied its high-affinity binding sites. in ventricular myocytes isolated from rats, cgp 20712a (10, 100, 1000 nm) didn’t cause the activation of adenylate cyclase mediated by β2-adrenoceptors, which suggested that β2-adrenoceptors were not present on rat ventricular myocytes [3]. in adult rat cardiac myocytes, cgp 20712a inhibited β1-ar-stimulated apoptosis, which was mediated by a camp-dependent mechanism [4].
References
[1]. dooley dj, bittiger h, reymann nc. cgp 20712 a: a useful tool for quantitating beta 1- and beta 2-adrenoceptors. eur j pharmacol, 1986, 130(1-2): 137-139.
[2]. chaudhry a, granneman jg. differential regulation of functional responses by beta-adrenergic receptor subtypes in brown adipocytes. am j physiol, 1999, 277(1 pt 2): r147-153.
[3]. kitagawa y, adachi-akahane s, nagao t. determination of beta-adrenoceptor subtype on rat isolated ventricular myocytes by use of highly selective beta-antagonists. br j pharmacol. 1995, 116(1): 1635-1643.
[4]. communal c, singh k, sawyer db, et al. opposing effects of beta(1)- and beta(2)-adrenergic receptors on cardiac myocyte apoptosis : role of a pertussis toxin-sensitive g protein. circulation, 1999, 100(22): 2210-2212.
