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首页> 外文期刊>Canadian Journal of Physiology and Pharmacology >Effect of asymmetry of concentration-response curves on the results obtained by the receptorial responsiveness method (RRM): an in silico study.
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Effect of asymmetry of concentration-response curves on the results obtained by the receptorial responsiveness method (RRM): an in silico study.

机译：浓度响应曲线的不对称性对通过受体响应方法（RRM）获得的结果的影响：计算机研究。

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The receptorial responsiveness method (RRM) was proposed to estimate changes in the concentration of an agonist in the microenvironment of its receptor. Usually, this is done by providing the equieffective concentration of another agonist for the same receptor or for a largely overlapping postreceptorial signaling ("test agonist"). The RRM is a special nonlinear regression algorithm to analyze a concentration-response (E/c) curve that represents the simultaneous actions of a single agonist concentration to be estimated and of increasing concentrations of the test agonist. The aim of this study was to explore whether asymmetry of the E/c curve to be analyzed influences the reliability of the RRM. For this purpose, computer simulation was performed by constructing symmetric and asymmetric E/c curves using the operational model of agonism, and then these curves were analyzed with the RRM. To perform the RRM, 2 types of equations were used: one involving the Hill equation, the simplest model of the E/c relationship, and one containing the Richards equation, an advanced model properly handling E/c curve asymmetry. Results of this study indicate that E/c curve asymmetry does not significantly influence the accuracy of the estimates provided by the RRM. Thus, when using the RRM, it is not necessary to replace the Hill equation with the Richards equation to obtain useful estimates. Furthermore, it was found that estimation of a high concentration of a high-efficacy agonist can fail when the RRM is performed with a low-efficacy test agonist in a system characterized by a small operational slope factor.
机译：提出了受体反应性方法（RRM）来估计其受体微环境中激动剂浓度的变化。通常，这是通过为相同的受体或在很大程度上重叠的受体后信号传导（“测试激动剂”）提供等效浓度的另一种激动剂来完成的。 RRM是一种特殊的非线性回归算法，用于分析浓度响应（E / c）曲线，该曲线表示要估计的单个激动剂浓度和测试激动剂浓度增加的同时作用。这项研究的目的是探讨要分析的E / c曲线的不对称性是否会影响RRM的可靠性。为此，使用激动作用的操作模型通过构建对称和不对称E / c曲线进行计算机仿真，然后使用RRM对这些曲线进行分析。为了执行RRM，使用了两种类型的方程：一种涉及Hill方程，这是最简单的E / c关系模型，而另一种包含Richards方程，这是一种正确处理E / c曲线不对称的高级模型。这项研究的结果表明，E / c曲线的不对称性不会显着影响RRM提供的估算值的准确性。因此，当使用RRM时，不必用Richards方程代替Hill方程以获得有用的估计。此外，发现当在以小工作斜率因子为特征的系统中用低效测试激动剂进行RRM时，高效率的激动剂的高浓度估计可能失败。

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