Liang B T, Molinoff P B
J Pharmacol Exp Ther. 1986 Sep;238(3):886-92.
The relationship between occupancy of beta adrenergic receptors and stimulation of adenylate cyclase in dog atrial tissue was examined by studying the binding of [125I]iodopindolol and the activation of adenylate cyclase. Computer-assisted nonlinear regression analysis was used to analyze the inhibition of isoproterenol-stimulated adenylate cyclase activity by beta-1- or beta-2-selective antagonists. The Ki values for each subtype of receptor for the selective antagonists resulting from studies of the inhibition of adenylate cyclase activity were similar to those determined in studies of the inhibition of the binding of [125I]iodopindolol. To compare further the occupancy of beta-1 or beta-2 adrenergic receptors with the activation of adenylate cyclase mediated by each class of receptor, computer modeling of the stimulation of adenylate cyclase by the beta-1-selective agonist norepinephrine was carried out. The EC50 values of norepinephrine for each receptor subtype, as measured in studies of norepinephrine-stimulated adenylate cyclase activity, were similar to the Ki values for the inhibition by norepinephrine of the binding of [125I]iodopindolol to each receptor subtype. The data led to the conclusion that beta-1 adrenergic receptors make up about 70% of the total number of beta adrenergic receptors and mediate 70% of the increase in adenylate cyclase activity produced by isoproterenol. These results suggest that the relationship between occupancy of each class of receptor and activation of adenylate cyclase is linear and that, when agonist-stimulated adenylate cyclase activity is used as a functional response, neither spare beta-1 nor spare beta-2 adrenergic receptors exist in the atrium.(ABSTRACT TRUNCATED AT 250 WORDS)
通过研究[125I]碘吲哚洛尔的结合以及腺苷酸环化酶的激活，考察了犬心房组织中β肾上腺素能受体占有率与腺苷酸环化酶刺激之间的关系。采用计算机辅助非线性回归分析来分析β1或β2选择性拮抗剂对异丙肾上腺素刺激的腺苷酸环化酶活性的抑制作用。由腺苷酸环化酶活性抑制研究得出的选择性拮抗剂对每种受体亚型的Ki值，与[125I]碘吲哚洛尔结合抑制研究中测定的值相似。为了进一步比较β1或β2肾上腺素能受体的占有率与每类受体介导的腺苷酸环化酶激活情况，对β1选择性激动剂去甲肾上腺素刺激腺苷酸环化酶进行了计算机建模。在去甲肾上腺素刺激的腺苷酸环化酶活性研究中测得的去甲肾上腺素对每种受体亚型的EC50值，与去甲肾上腺素抑制[125I]碘吲哚洛尔与每种受体亚型结合的Ki值相似。这些数据得出结论，β1肾上腺素能受体约占β肾上腺素能受体总数的70%，并介导异丙肾上腺素产生的腺苷酸环化酶活性增加的70%。这些结果表明，每类受体的占有率与腺苷酸环化酶激活之间的关系是线性的，并且，当激动剂刺激的腺苷酸环化酶活性用作功能反应时，心房中不存在备用的β1或β2肾上腺素能受体。（摘要截短于250字）
