Venter D P, Brink C B
Department of Pharmacology, Potchefstroom University for Christian Higher Education, South Africa.
Eur J Pharmacol. 1998 May 29;350(1):109-20. doi: 10.1016/s0014-2999(98)00219-2.
It was shown in previous studies that fixed ratio combinations of agonists with competitive antagonists emulate partial agonists and, therefore, mediate submaximal concentration-effect (E/[A]) curves. A linear plot was obtained by plotting the relative height (H) of these submaximal curves against phiH, where phi=[antagonist]/[agonist]. In this study, it was shown that in an agonist-effector system comprising a possible threshold value, the use of fixed ratio agonist-competitive antagonist concentrations (artificial partial agonists) induces E/[A] curves of different heights which allows one to quantify the threshold value. A nonlinear parabolic-like plot may be obtained when a threshold value is present in an agonist-effector system. By quantifying the threshold value, the nonlinear plot was converted to a linear plot from which the apparent affinity (KA) and an efficacy related parameter (eES) of an agonist could be estimated. The practical applicability of the method was shown by applying the method to E/[A] curves obtained for agonists (noradrenaline and acetylcholine) obtained in the presence and absence of increasing concentrations of their respective competitive antagonists on different effectors.
先前的研究表明，激动剂与竞争性拮抗剂的固定比例组合可模拟部分激动剂，因此介导次最大浓度 - 效应（E/[A]）曲线。通过将这些次最大曲线的相对高度（H）对φH作图可得到线性图，其中φ = [拮抗剂]/[激动剂]。在本研究中，表明在一个可能包含阈值的激动剂 - 效应器系统中，使用固定比例的激动剂 - 竞争性拮抗剂浓度（人工部分激动剂）会诱导出不同高度的E/[A]曲线，这使得人们能够对阈值进行量化。当激动剂 - 效应器系统中存在阈值时，可能会得到非线性抛物线状图。通过对阈值进行量化，可将非线性图转换为线性图，从中可以估计激动剂的表观亲和力（KA）和一个与效能相关的参数（eES）。通过将该方法应用于在不同效应器上分别存在和不存在各自竞争性拮抗剂浓度增加时获得的激动剂（去甲肾上腺素和乙酰胆碱）的E/[A]曲线，展示了该方法的实际适用性。
