Niclauss Nadja, Michel-Reher Martina B, Alewijnse Astrid E, Michel Martin C
Department Pharmacology and Pharmacotherapy, Academic Medical Center, University of Amsterdam, Meibergdreef 15, Amsterdam, The Netherlands.
Naunyn Schmiedebergs Arch Pharmacol. 2006 Nov;374(2):99-105. doi: 10.1007/s00210-006-0104-z. Epub 2006 Oct 7.
We have compared the ability of three radioligands, [(125)I]-cyanopindolol, [(3)H]-CGP 12,177 and [(3)H]-dihydroalprenolol, to label the three human beta-adrenoceptor subtypes. Saturation and competition binding experiments were performed using membrane preparations from Chinese hamster ovary cells stably transfected with the three subtypes. While [(3)H]-CGP 12,177 had very similar affinity for beta(1)- and beta(2)-adrenoceptors (about 40 pM), [(125)I]-cyanopindolol and [(3)H]-dihydroalprenolol had 4- to 6-fold higher affinity for beta(2)- as compared to beta(1)-adrenoceptors (10 vs 45 and 187 vs 1,021 pM, respectively). The affinity of [(125)I]-cyanopindolol at beta(3)-adrenoceptors was considerably lower (440 pM) than at the other two subtypes. The beta(3)-adrenoceptor affinity of [(3)H]-CGP 12,177 and [(3)H]-dihydroalprenolol was so low that it could not be estimated within the tested range of radioligand concentrations (up to 4,000 pM and 30,000 pM for [(3)H]-CGP 12,177 and [(3)H]-dihydroalprenolol, respectively). We conclude that all three radioligands are ill-suited to label beta(3)-adrenoceptors, particularly in preparations co-expressing multiple subtypes. In the absence of alternatives, [(125)I]-cyanopindolol appears the least unsuitable to label beta(3)-adrenoceptors. There is a need for high-affinity radioligands which are either selective for beta(3)-adrenoceptors or reasonably non-selective among all three beta-adrenoceptor subtypes.
我们比较了三种放射性配体，即[（125）I] - 氰基吲哚洛尔、[（3）H] - CGP 12177和[（3）H] - 二氢烯丙洛尔，标记三种人类β - 肾上腺素能受体亚型的能力。使用稳定转染了这三种亚型的中国仓鼠卵巢细胞的膜制剂进行了饱和与竞争结合实验。虽然[（3）H] - CGP 12177对β（1） - 和β（2） - 肾上腺素能受体具有非常相似的亲和力（约40 pM），但[（125）I] - 氰基吲哚洛尔和[（3）H] - 二氢烯丙洛尔对β（2） - 肾上腺素能受体的亲和力比对β（1） - 肾上腺素能受体高4至6倍（分别为10对45以及187对1021 pM）。[（125）I] - 氰基吲哚洛尔对β（3） - 肾上腺素能受体的亲和力（440 pM）明显低于对其他两种亚型的亲和力。[（3）H] - CGP 12177和[（3）H] - 二氢烯丙洛尔对β（3） - 肾上腺素能受体的亲和力非常低，以至于在测试的放射性配体浓度范围内（[（3）H] - CGP 12177和[（3）H] - 二氢烯丙洛尔分别高达4000 pM和30000 pM）无法进行估算。我们得出结论，所有这三种放射性配体都不适于标记β（3） - 肾上腺素能受体，尤其是在共表达多种亚型的制剂中。在没有其他选择的情况下，[（125）I] - 氰基吲哚洛尔似乎是标记β（3） - 肾上腺素能受体最不不合适的。需要有对β（3） - 肾上腺素能受体具有选择性或在所有三种β - 肾上腺素能受体亚型中具有合理非选择性的高亲和力放射性配体。
