Eskelinen S
Department of Physiology, University of Oulu, Finland.
Can J Physiol Pharmacol. 1987 Dec;65(12):2373-8. doi: 10.1139/y87-376.
The time course of the shape transformations and vesicle release in human erythrocytes caused by lysophosphatidylcholine and chlorpromazine was monitored using a light microscope-video recording technique. The time required for the erythrocytes to reach a stage I echinocytic shape decreased from 4.0 to 2.0 s, when the concentration of the lysophosphatidylcholine solution injected was increased from 1 to 25 microM. The time required to reach stage II decreased from 8.3 to 3.5 s and that required for vesicle release and the formation of stage IV spherocytes decreased from 78.0 to 11.6 s. Correspondingly, the time needed for the formation of stage I stomatocytes decreased from 2.3 to 1.0 s and that for stage II stomatocytes from 3.1 to 2.0 s, when the ambient chlorpromazine concentration was increased from 50 to 200 microM. The kinetics of the shape transformations of the erythrocytes were dependent on the ambient drug concentration. The rate of shape transformations could be predicted from a formula derived for the kinetics of the incorporation of the detergent into the cell membrane, providing that the affinity coefficient and mass transfer coefficient for drugs changed as a function of the free drug concentration. The results give a time scale for the drug-membrane interactions, i.e., the formation of stages I and II for drug-lipid bilayer interactions and the release of vesicles for drug-cytoskeleton interactions.
采用光学显微镜-视频记录技术监测溶血磷脂酰胆碱和氯丙嗪引起的人红细胞形状转变和囊泡释放的时间进程。当注入的溶血磷脂酰胆碱溶液浓度从1 microM增加到25 microM时，红细胞达到I期棘状细胞形状所需的时间从4.0秒降至2.0秒。达到II期所需的时间从8.3秒降至3.5秒，囊泡释放和IV期球形红细胞形成所需的时间从78.0秒降至11.6秒。相应地，当环境氯丙嗪浓度从50 microM增加到200 microM时，I期口形细胞形成所需的时间从2.3秒降至1.0秒，II期口形细胞形成所需的时间从3.1秒降至2.0秒。红细胞形状转变的动力学取决于环境药物浓度。只要药物的亲和系数和传质系数随游离药物浓度变化，形状转变速率就可以从为洗涤剂掺入细胞膜动力学推导的公式中预测。结果给出了药物-膜相互作用的时间尺度，即药物-脂质双层相互作用的I期和II期形成以及药物-细胞骨架相互作用的囊泡释放。
