Obligatory separation of hormone binding and biological response curves in systems dependent upon secondary mediators of hormone action.
Obligatory separation of hormone binding and biological response curves in systems dependent upon secondary mediators of hormone action.
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系统中激素结合和生物反应曲线的强制性分离取决于激素作用的次要介质。
DOI：
10.1073/pnas.78.3.1366
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发表时间：
1981
影响因子：
11.1
通讯作者：
Loeb,JN
中科院分区：
文献类型：
--
作者：
Strickland,S;Loeb,JN
提出了一个数学模型，描述了激素浓度对受体饱和度和生物反应的影响，系统中依赖于第二介质（如环磷酸腺苷）的产生。该分析做出以下假设：（i）激素与其受体的结合是可逆的二级反应； (ii)产生的介质浓度与激素占据的膜结合位点的数量成正比； (iii)介体与其胞内受体结合产生效应复合物也是二阶的，并导致相应的生物反应。从这种处理可以看出，半最大生物反应所需的激素浓度在形式上低于半最大受体饱和所需的激素浓度，并且这两个浓度之间的差异将取决于在完全受体占据时产生的总介体与介体与其受体的解离常数的比率。在不援引负协同性概念的情况下，该模型为经常观察到的受体占据和生物反应曲线之间的差异提供了简单的解释。此外，预测的生物响应曲线的数学形式符合在各种系统中通过实验观察到的响应曲线的形状。
A mathematical model is presented that describes the effects of hormone concentration on receptor saturation and biological response in systems dependent upon the generation of a secondary mediator such as cyclic AMP. The analysis makes the following assumptions: (i) the binding of hormone to its receptor is a reversible, second-order reaction; (ii) the concentration of mediator that is generated is directly proportional to the number of membrane binding sites occupied by hormone; and (iii) the binding of the mediator with its intracellular receptor to generate an effector complex is also second-order and results in a proportionate biological response. It follows from this treatment that the hormone concentration required for half-maximal biological response is formally lower than that required for half-maximal receptor saturation and that the difference between these two concentrations will depend upon the ratio of total mediator generated at full receptor occupancy to the dissociation constant of the mediator with its receptor. Without invoking concepts of negative cooperativity, this model offers a simple explanation for discrepancies between receptor occupancy and biological response curves that are often observed. Moreover, the mathematical form of the predicted biological response curves conforms to the shape of the response curves observed experimentally in a wide variety of systems.
DOI：
10.1038/newbio244219a0
发表时间：
1973-01-01
期刊：
NATURE-NEW BIOLOGY
影响因子：
--
作者：
CATT, KJ;DUFAU, ML
通讯作者：
DUFAU, ML
DOI：
10.1016/s0006-291x(73)80072-5
发表时间：
1973-01-01
影响因子：
3.1
作者：
DEMEYTS, P;ROTH, J;LESNIAK, MA
通讯作者：
LESNIAK, MA