Quantitative analysis of the selectivity of radioligands for subtypes of beta adrenergic receptors.
Quantitative analysis of the selectivity of radioligands for subtypes of beta adrenergic receptors.
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发表时间：
1986-07
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通讯作者：
K. Neve;P. Mcgonigle;P. Molinoff
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作者：
K. Neve;P. Mcgonigle;P. Molinoff
在具有两类药物结合位点的组织中，通常通过抑制放射性配体与选择性未标记配体的结合来估计每类结合位点的比例。然而，只有当放射性配体是非选择性的或以使两类结合位点饱和的浓度使用时，才能获得每类结合位点密度的准确估计。使用PROPHET系统上的程序MLAB对多重抑制曲线进行同时回归分析的方法，用于定量放射性配体对β-1或β-2肾上腺素能受体的选择性。[125 I]碘吲哚洛尔、[125 I]碘氰基吲哚洛尔、[125 I]碘羟基苄基吲哚洛尔和[3 H]二氢烯丙洛尔对β-1和β-2肾上腺素能受体的选择性通过使用由C6神经胶质瘤细胞制备的膜，在放射性配体浓度增加时抑制每种放射性配体与β-1-选择性未标记配体ICI 89，406的结合来评估，其具有β-1和β-2肾上腺素能受体。所有四种放射性配体的Scatchard图呈线性，相关系数大于0.95。[125 I]碘吲哚洛尔和[125 I]碘氰基吲哚洛尔对β-2肾上腺素能受体的选择性分别为3.2倍和2倍，[125 I]碘羟基苄基吲哚洛尔和[3 H]二氢烯丙洛尔对β-2肾上腺素能受体的选择性分别为5.8倍和2.3倍。β-1和β-2肾上腺素能受体的密度值以及ICI 89，406受体的亲和力与所用的放射性配体无关。（250字处删节）
In tissues with two classes of binding sites for a drug, it is common to estimate the proportion of each class of binding site by inhibiting the binding of a radioligand with a selective unlabeled ligand. Accurate estimates of the density of each class of binding site, however, will be obtained only if the radioligand is nonselective or used at a concentration that saturates both classes of binding sites. A method of simultaneous regression analysis of multiple inhibition curves, using the program MLAB on the PROPHET system, was used to quantify the selectivity of radioligands for beta-1 or beta-2 adrenergic receptors. The selectivity of [125I]iodopindolol, [125I]iodocyanopindolol, [125I]iodohydroxybenzylpindolol and [3H]dihydroalprenolol for beta-1 and beta-2 adrenergic receptors was assessed by inhibiting the binding of each radioligand with the beta-1-selective unlabeled ligand ICI 89,406 at increasing concentrations of the radioligand, using membranes prepared from C6 glioma cells, which have both beta-1 and beta-2 adrenergic receptors. Scatchard plots for all four radioligands were linear, with correlation coefficients greater than 0.95. [125I]Iodopindolol and [125I]iodocyanopindolol were 3.2- and 2-fold selective, respectively, and [125I]iodohydroxybenzylpindolol and [3H]dihydroalprenolol were 5.8- and 2.3-fold selective, respectively, for beta-2 adrenergic receptors. Values obtained for the densities of beta-1 and beta-2 adrenergic receptors and the affinities of the receptors for ICI 89,406 were independent of the radioligand used.(ABSTRACT TRUNCATED AT 250 WORDS)