Kenakin T P, Morgan P H
Department of Molecular Pharmacology, Glaxo Research Laboratories, Research Triangle Park, North Carolina 27709.
Mol Pharmacol. 1989 Feb;35(2):214-22.
A mathematical model is presented that simulates the steady state kinetics of agonists interacting with a promiscuous receptor. The model system consists of a single receptor that forms a ternary complex with either of two transducer proteins (G proteins). At a given agonist concentration, the concentrations of the two ternary complexes are determined by the relative quantities of the two G proteins and the ratio of the dissociation constants for the two ternary complexes. Accordingly, the potency of an agonist is dependent upon the relative quantities of the G proteins. If receptors are truly promiscuous and if the distribution of G proteins varies with tissue type, then the agonist potency ratio would be tissue dependent as well as receptor dependent. Experimental data from literature studies are reviewed in the context of the promiscuous receptor model, and implications of the model regarding pharmacologic classification of receptors are discussed.
本文提出了一个数学模型，用于模拟激动剂与混杂型受体相互作用的稳态动力学。该模型系统由一个单一受体组成，该受体与两种转导蛋白（G蛋白）中的任何一种形成三元复合物。在给定的激动剂浓度下，两种三元复合物的浓度由两种G蛋白的相对量以及两种三元复合物解离常数的比值决定。因此，激动剂的效力取决于G蛋白的相对量。如果受体确实是混杂型的，并且G蛋白的分布随组织类型而变化，那么激动剂效力比值将既取决于组织也取决于受体。本文在混杂型受体模型的背景下回顾了文献研究中的实验数据，并讨论了该模型对受体药理学分类的意义。
