McPherson G A, Molenaar P, Raper C, Malta E
J Pharmacol Methods. 1983 Dec;10(4):231-41. doi: 10.1016/0160-5402(83)90017-7.
The KA value of a full agonist (Furchgott, 1966) is usually calculated following the transformation of a rectangular hyperbolic relationship between equiactive concentrations into a linear relationship via a double reciprocal plot. Such a transformation will introduce error into the value of KA unless the pre- and postinactivation dose-response curves are also rectangular hyperbolas. Nonlinear curve fitting computer programs, which have been developed to evaluate radioligand binding data, fit data to rectangular hyperbolas and, thus, can be used to fit concentration-response data for pre- and postinactivation curves. Examination of (-)-isoprenaline concentration-response curves for positive inotropic effects in left atrial preparations from the guinea pig, established before and after treatment with the irreversible antagonist Ro 03-7894, indicated a marked deviation from the theoretical rectangular hyperbola (Hill coefficient greater than 1). This was accounted for by the presence of a threshold effect. The present study reports on the use of the computer program LIGAND to fit a rectangular hyperbola to the pre- and postinactivation curves for an agonist, while simultaneously calculating and allowing for the presence of a threshold phenomenon. Since both curves are fitted to rectangular hyperbolas, the KA values can be calculated with greater precision than that possible from double reciprocal plots constructed from uncorrected concentration-response curves.
完全激动剂的KA值（Furchgott，1966）通常是在将等活性浓度之间的矩形双曲线关系通过双倒数图转化为线性关系之后进行计算。除非失活前后的剂量反应曲线也是矩形双曲线，否则这种转化会给KA值引入误差。为评估放射性配体结合数据而开发的非线性曲线拟合计算机程序，可将数据拟合成矩形双曲线，因此可用于拟合失活前后曲线的浓度反应数据。对豚鼠左心房制备物中（-）-异丙肾上腺素正性肌力作用的浓度反应曲线进行检查，该曲线是在使用不可逆拮抗剂Ro 03 - 7894处理前后建立的，结果表明该曲线明显偏离理论矩形双曲线（希尔系数大于1）。这是由阈值效应的存在导致的。本研究报告了使用计算机程序LIGAND将矩形双曲线拟合到激动剂失活前后的曲线，同时计算并考虑阈值现象的存在。由于两条曲线都被拟合成矩形双曲线，因此与根据未校正的浓度反应曲线构建的双倒数图相比，KA值可以更精确地计算出来。
