DRUG-INDUCED ERYTHROCYTE-MEMBRANE INTERNALIZATION
DRUG-INDUCED ERYTHROCYTE-MEMBRANE INTERNALIZATION
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DOI：
10.1172/jci106985
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发表时间：
1972-01-01
影响因子：
15.9
通讯作者：
SCHRIER, SL
中科院分区：
文献类型：
--
作者：
BENBASSAT, I;BENSCH, KG;SCHRIER, SL
在体外红细胞膜内化，导致膜内衬空泡的形成，可以通过放射性同位素方法定量。37 Co标记的维生素B12及其血浆蛋白结合剂的复合物首先吸附到细胞表面，在形成空泡后，通过洗涤和胰蛋白酶处理除去未内化的标记物。残留的放射性代表捕获的标签，并可用于测量膜internalization.Using这种方法的程度，它被发现，除了伯氨喹，一组膜活性药物，特别是氢化可的松，长春碱，氯丙嗪可以诱导红细胞膜内化。这是一个依赖于药物浓度、温度和pH值的代谢过程。所有受试药物的胆固醇形成均可通过内源性底物的预先消耗或通过氟化钠和巯基封闭剂使红细胞中毒而被阻断。这种现象在某些方面类似于以前报道的膜内化的通电红细胞血影。有人建议，膜内化是依赖于ATP-通电状态，并受到膜中的镁和钙的浓度之间的平衡。这项研究为提出一些膜活性药物作用的统一概念以及考虑红细胞膜内化在病理生理事件中的作用提供了基础。图片
In vitro erythrocyte membrane internalization, resulting in the formation of membrane-lined vacuoles, can be quantified by a radioisotopic method. A complex of37Co-labeled vitamin B12and its plasma protein binders is first adsorbed to the cell surface, and after vacuoles are formed, the noninternalized label is removed by washing and trypsin treatment. The residual radioactivity represents trapped label and can be used to measure the extent of membrane internalization.Using this method, it was found that in addition to primaquine, a group of membrane-active drugs, specifically hydrocortisone, vinblastine, and chlorpromazine can induce membrane internalization in erythrocytes. This is a metabolic process dependent on drug concentration, temperature, and pH. Vacuole formation by all agents tested can be blocked by prior depletion of endogenous substrates or by poisoning the erythrocytes with sodium fluoride and sulfhydryl blocking agents. This phenomenon resembles in some respects the previously reported membrane internalization of energized erythrocyte ghosts. It is suggested that membrane internalization is dependent on an ATP-energized state and is influenced by the balance between the concentrations of magnesium and calcium in the membrane. This study provides a basis for proposing a unifying concept of the action of some membrane-active drugs, and for considering the role of erythrocyte membrane internalization in pathophysiologic events.Images