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一种体外预筛选评估有毒金属离子与常见金属离子之间关系的新方法。

A new method of in vitro prescreening evaluation of the relationship between toxic and common metal ions.

作者信息

Bara M, Guiet-Bara A, Durlach J

机构信息

Laboratory of Biology of Reproduction, University P.M. Curie, Paris, France.

出版信息

Methods Find Exp Clin Pharmacol. 1992 May;14(4):311-4.

PMID:1507934
Abstract

The human amniotic membrane, an asymmetrical and nonexcitable epithelium with sites differently situated on the fetal and maternal sides, may be considered a model for investigating the relationship between toxic and common metal ions. The method is based on the observation of the ionic transfer across the amnion, estimated by measuring the total ionic conductance Gt from the mother to the fetus and from the fetus to the mother. It is important to note that opposite effects between two ions are not necessarily correlated with antagonism; indeed, pollutants decrease ionic conductance Gt and Mg increases it, but Mg is not an antagonist of all pollutants. To define antagonism between two ions, the Dixon curves theory should be applied. These curves represent the variation of Gt when the concentration of common metal increases (1 mM, 3 mM), while the concentration of toxic metal is maintained constant (3 concentrations of toxic metal are used). The straight lines obtained are either parallel to each other (noncompetitive inhibition), parallel to the x axis (no interaction between common and toxic metals), or the 3 lines intersect at a common point equal to the inhibition constant. At pharmacological doses, there is competitive inhibition (specific antagonism) between Mg and Cd, Zn and Cd, Ca and Cd, and Mg and Pb, and noncompetitive inhibition between Mg and Hg. This method may rapidly indicate a membrane interaction between common and toxic metals.

摘要

人羊膜是一种不对称且不可兴奋的上皮组织,在胎儿侧和母体侧的位置不同,可被视为研究有毒金属离子与常见金属离子之间关系的模型。该方法基于对羊膜离子转运的观察,通过测量从母体到胎儿以及从胎儿到母体的总离子电导Gt来估算。需要注意的是,两种离子之间的相反作用不一定与拮抗作用相关;实际上,污染物会降低离子电导Gt,而镁会增加离子电导Gt,但镁并非所有污染物的拮抗剂。为了定义两种离子之间的拮抗作用,应应用迪克森曲线理论。这些曲线表示当常见金属浓度增加(1 mM、3 mM),而有毒金属浓度保持恒定时(使用3种有毒金属浓度)Gt的变化。得到的直线要么相互平行(非竞争性抑制),要么与x轴平行(常见金属和有毒金属之间无相互作用),要么3条线在等于抑制常数的共同点相交。在药理剂量下,镁与镉、锌与镉、钙与镉以及镁与铅之间存在竞争性抑制(特异性拮抗),而镁与汞之间存在非竞争性抑制。该方法可以快速表明常见金属和有毒金属之间的膜相互作用。

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