McGonigle P
Department of Pharmacology, University of Pennsylvania, Philadelphia 19104-6084.
J Cardiovasc Pharmacol. 1988;11 Suppl 1:S73-7.
Many radioligands used to study neurotransmitter receptors label multiple subtypes or multiple classes of receptors. Frequently, two subtypes or classes of receptors coexist in the same tissue and exhibit only slightly different affinities for a radioligand. A new analytical method has been developed to quantitate the interaction of a slightly selective radioligand with two distinct classes of binding sites. This new approach requires that a series of inhibition experiments with a selective unlabeled ligand be performed in the presence of increasing concentrations of the radioligand. Analysis of the resulting inhibition curves, utilizing simultaneous nonlinear regression analysis techniques, yields estimates of the density of each class of receptor as well as the affinity of each receptor for the labeled and unlabeled ligands. This approach was used to characterize the interaction of [3H]spiroperidol with serotonin 5-HT2 and dopamine D2 receptors. A series of inhibition curves were generated with the 5-HT2 selective antagonist ketanserin using membranes prepared from rat striatum. [3H]Spiroperidol was found to be 23-fold more selective for D2 receptors and 27% of the sites labeled by [3H]spiroperidol exhibited a high affinity for ketanserin and were presumed to be 5-HT2 receptors. Since all of the radioligands commonly used to label 5-HT2 receptors also label other receptors, this method of analysis should be particularly useful in the study of these receptors.
许多用于研究神经递质受体的放射性配体可标记多种亚型或多类受体。通常，两种受体亚型或类别共存于同一组织中，并且对放射性配体的亲和力仅略有不同。已开发出一种新的分析方法，用于定量一种选择性稍差的放射性配体与两类不同结合位点的相互作用。这种新方法要求在放射性配体浓度不断增加的情况下，用一种选择性未标记配体进行一系列抑制实验。利用同步非线性回归分析技术对所得抑制曲线进行分析，可得出每类受体的密度估计值以及每种受体对标记和未标记配体的亲和力。该方法用于表征[3H]螺哌啶醇与5-羟色胺5-HT2和多巴胺D2受体的相互作用。使用从大鼠纹状体制备的膜，用5-HT2选择性拮抗剂酮色林生成了一系列抑制曲线。发现[3H]螺哌啶醇对D2受体的选择性高23倍，[3H]螺哌啶醇标记的位点中有27%对酮色林表现出高亲和力，推测为5-HT2受体。由于所有常用于标记5-HT2受体的放射性配体也标记其他受体，因此这种分析方法在这些受体的研究中应特别有用。
