APPLICATION OF THE OPERATIONAL MODEL OF AGONISM TO ESTABLISH CONDITIONS WHEN FUNCTIONAL ANTAGONISM MAY BE USED TO ESTIMATE AGONIST DISSOCIATION-CONSTANTS
APPLICATION OF THE OPERATIONAL MODEL OF AGONISM TO ESTABLISH CONDITIONS WHEN FUNCTIONAL ANTAGONISM MAY BE USED TO ESTIMATE AGONIST DISSOCIATION-CONSTANTS
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DOI：
10.1111/j.1476-5381.1985.tb10561.x
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发表时间：
1985-01-01
影响因子：
7.3
通讯作者：
MORSE, JM
中科院分区：
文献类型：
--
作者：
LEFF, P;MARTIN, GR;MORSE, JM
激动作用的操作模型（Black和Leff）用于分析比较功能性拮抗作用和不可逆拮抗作用，作为估计激动剂解离常数（Ka）的方法。一个一般的条件是建立在模型参数，它定义了实验干预的类型在受体和postreceptor水平，允许有效的Ka估计。功能性拮抗作用和其他受体后干预可能会产生激动剂浓度效应曲线的变化，这些变化在定性上无法区分，但在定量上与不可逆拮抗作用产生的变化不同。用豚鼠气管条制备获得的实验数据与理论预测一致，并表明使用功能性拮抗作用的研究可能高估激动剂亲和力。一般而言，功能性拮抗作用与不可逆拮抗作用不同，原则上是一种不可靠的定量激动作用的方法。[The激素和药物的激动剂活性进行了讨论。
The operational model of agonism (Black and Leff) was used to analyse comparatively functional antagonism and irreversible antagonism as methods for estimating agonist dissociation constants (Ka). A general condition is established in terms of the model parameters which defines the type of experimental interventions at the receptor and the postreceptor level that allow valid Ka estimation. Functional antagonism and other postreceptor interventions may produce changes in agonist-concentration effect curves which are qualitatively indistinguishable but quantitatively distinct, from those produced by irreversible antagonism. Experimental data obtained with the guinea pig tracheal strip preparation are in keeping with the theoretical predictions and show how studies using functional antagonism may overestimate agonist affinity. In general, functional antagonism, unlike irreversible antagonism, is in principle an unreliable method for quantifying agonism. [The agonist activity of hormones and drugs is discussed.].