CGP 20712 dihydrochloride

CGP 20712 dihydrochloride是一种强效的和选择性的β1肾上腺素受体拮抗剂,IC50值为0.7 nM [1].

β1肾上腺素受体是一种G蛋白偶联受体,并介导去甲肾上腺素(NE)诱导的解偶联蛋白-1(UCP1)基因表达[2].

CGP 20712 dihydrochloride是一种强效的和选择性的β1肾上腺素受体拮抗剂.在新皮质膜中,CGP 20712 A表现出对β1肾上腺素受体和β2肾上腺素受体的亲和力,IC50值分别为0.7和6700 nM [1].在褐色脂肪细胞中,CGP-20712A显著抑制NE诱导的UCP1基因表达.然而,CGP-20712A对脂肪分解无影响.这些结果表明,β1肾上腺素受体介导UCP1基因表达[2].在大鼠心室膜中,CGP 20712A(300 nM)完全占据其高亲和力的结合位点.在分离的大鼠心肌细胞中,CGP 20712A(10\100\1000 nM)未引起β2肾上腺素受体介导的腺苷酸环化酶的激活,这表明β2肾上腺素受体不存在于大鼠心肌细胞[3].在成年大鼠心肌细胞中,CGP 20712A抑制β1-AR刺激的细胞凋亡,这是由cAMP依赖性的机制介导的[4].

参考文献：
[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.