Apparent positive cooperative effects in cyclic AMP and corticosterone production by isolated adrenal cells in response to ACTH analogues.

Apparent positive cooperative effects in cyclic AMP and corticosterone production by isolated adrenal cells in response to ACTH analogues.
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分离的肾上腺细胞对 ACTH 类似物的反应对环 AMP 和皮质酮产生有明显的积极协同作用。

DOI:
10.1210/endo-94-5-1427
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发表时间:
1974
期刊:
影响因子:
4.8
通讯作者:
D. Rodbard
D. Rodbard
中科院分区:
医学2区
文献类型:
--
作者:
D. Rodbard

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本文用ACTH_(1 -24)和一些ACTH类似物对离体大鼠肾上腺皮质细胞产生cAMP和皮质酮的量效曲线进行了测定。本文提出了一种新的拟合Hill方程模拟物参数的方法,即采用加权迭代非线性最小二乘回归法,该方法能够估计对零剂量(“对照”)的反应、对“无限剂量”(“Vmax”)的反应、ED_(50)或“Km”以及“Hill系数”。该分析表明cAMP产生的平均希尔系数为1.33 ± 0.04,皮质酮产生的平均希尔系数为1.41 ± 0.07。这些结果提示在ACTH作用机制的一个或多个步骤中存在明显的正协同效应(可能是由于变构作用)。这些结果也与激素作用的修改后的“量子反应”模型相一致。这些结果似乎不符合简单的“米氏”动力学或与一个机制,涉及两个简单的米氏类型的反应…
Dose-response curves were con-structed for production of cAMP and corticosterone by isolated cells from rat adrenal cortex in response to ACTH1–24 and a number of ACTH analogues. A new method for fitting the parameters of an analogue of the Hill equation was developed, using a weighted iterative nonlinear least squares regres-sion capable of estimating both the response to zero dose (“control”), the response to “infinite dose” (“Vmax”), the ED50 or “Km”, and the “Hill coefficient.” This analysis indicates a mean Hill coefficient of 1.33 ± 0.04 for cAMP production and 1.41 ± 0.07 for corticosterone production. These results are suggestive of an apparent positive cooperative effect (possibly due to allosterism) at one or more steps in the mechanism of action of ACTH. These results are also compatible with a modified “quantal response” model of hormone action. These results appear inconsistent with simple “Michaelis-Menten” kinetics or with a mechanism involving two simple Michaelis-Menten type reactions in ...