ESTIMATION OF COMPETITIVE ANTAGONIST AFFINITY FROM FUNCTIONAL INHIBITION CURVES USING THE GADDUM, SCHILD AND CHENG-PRUSOFF EQUATIONS
ESTIMATION OF COMPETITIVE ANTAGONIST AFFINITY FROM FUNCTIONAL INHIBITION CURVES USING THE GADDUM, SCHILD AND CHENG-PRUSOFF EQUATIONS
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DOI：
10.1111/j.1476-5381.1993.tb13737.x
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发表时间：
1993-08-01
影响因子：
7.3
通讯作者：
BIRDSALL, NJM
中科院分区：
文献类型：
--
作者：
LAZARENO, S;BIRDSALL, NJM
1从功能实验中估算拮抗剂亲和力，其中固定激动剂浓度的效应被一系列拮抗剂浓度降低从理论和实验的角度考虑了（“功能抑制曲线”）。2将理论预测与乙酰胆碱刺激[S-35]-GTP γ S与中国仓鼠卵巢（CHO）膜结合获得的结果进行了比较。用人m1-m4毒蕈碱受体稳定转染的细胞，以及哌仑西平和AQ-RA 741对刺激结合的抑制。3应用Cheng-Prusoff校正的通常程序在理论上是无效的，并且预测了与该程序相关的误差的大小和分布。4用于估计拮抗剂亲和力的不同程序，发现使用剂量比分析的原理和类似于使用Gaddum方程是准确的和理论上有效的。5一种新的分析方法允许准确估计拮抗剂亲和力和Schild斜率，通过将来自拮抗剂抑制曲线和激动剂激活曲线的组合数据直接拟合到Schild方程的形式（由Waud推导）。6结果表明，可以通过将部分数据作为抑制曲线族处理并在Schild图中包括从抑制曲线估计的剂量比来增强常规Schild分析。
1 The estimation of antagonist affinity from functional experiments in which the effect of a fixed agonist concentration is reduced by a range of antagonist concentrations ('functional inhibition curves') has been considered from both a theoretical and experimental viewpoint.2 Theoretical predictions are compared with results obtained from the stimulation of [S-35]-GTPgammaS binding by acetylcholine to membranes of Chinese hamster ovary (CHO) cells stably transfected with human ml-m4 muscarinic receptors, and inhibition of the stimulated binding by pirenzepine and AQ-RA 741.3 The usual procedure of applying the Cheng-Prusoff correction is shown to be theoretically invalid, and predictions are made of the size and distribution of errors associated with this procedure.4 A different procedure for estimating antagonist affinity, using the principles of dose-ratio analysis and analogous to use of the Gaddum equation, is found to be accurate and theoretically valid.5 A novel method of analysis allows accurate estimation of both antagonist affinity and Schild slope, by fitting the combined data from an antagonist inhibition curve and an agonist activation curve directly to a form of the Schild equation (derived by Waud) using non-linear regression analysis.6 It is shown that the conventional Schild analysis can be enhanced by treating part of the data as a family of inhibition curves and including in the Schild plot dose-ratios estimated from the inhibition curves.