Poste G, Papahadjopoulos D, Jacobson K, Vail W J
Biochim Biophys Acta. 1975 Jul 18;394(4):520-39. doi: 10.1016/0005-2736(75)90138-8.
Treatment of untransformed mouse and hamster cells with the tertiary amine local anesthetics dibucaine, tetracaine and procaine increases their susceptibility to agglutination by low doses of the plant lectin concanavalin A. Agglutination of anesthetic-treated untransformed cells by low doses of concanavalin A is accompanied by redistribution of concanavalin A receptors on the cell surface to form patches, similar to that occurring in spontaneous agglutination of virus-transformed cells by concanavalin A. Immunofluorescence and freeze-fracture electronmicroscopic observations indicate that local anesthetics per se do not induce this redistribution of concanavalin A receptors but modify the plasma membrane so that receptor redistribution is facilitated on binding of concanavalin A to the cell surface. Fluorescence polarization measurements on the rotational freedom of the membrane-associated probe, diphenylhexatriene, indicate that local anesthetics produce a small increase in the fluidity of membrane lipids. Spontaneous agglutination of transformed cells by low doses of concanavalin A is inhibited by colchicine and vinblastine but these alkaloids have no effect on concanavalin A agglutination of anesthetic-treated cells. Evidence is presented which suggests that local anesthetics may impair membrane peripheral proteins sensitive to colchicine (microtubules) and cytochalasin-B (microfilaments). Combined treatment of untransformed 3T3 cells with colchicine and cytochalasin B mimics the effect of local anesthetics in enhancing susceptibility to agglutination by low doses of concanavalin A. A hypothesis is presented on the respective roles of colchicine-sensitive and cytochalasin B-sensitive peripheral membrane proteins in controlling the topographical distribution of lectin receptors on the cell surface.
用叔胺类局部麻醉药丁卡因、丁哌卡因和普鲁卡因处理未转化的小鼠和仓鼠细胞,可增加它们对低剂量植物凝集素刀豆球蛋白A凝集作用的敏感性。低剂量刀豆球蛋白A对经麻醉处理的未转化细胞的凝集作用,伴随着细胞表面刀豆球蛋白A受体重新分布形成斑块,这与刀豆球蛋白A对病毒转化细胞的自发凝集作用中发生的情况类似。免疫荧光和冷冻断裂电子显微镜观察表明,局部麻醉药本身不会诱导刀豆球蛋白A受体的这种重新分布,但会改变质膜,使得刀豆球蛋白A与细胞表面结合时受体重新分布更容易发生。对膜相关探针二苯基己三烯旋转自由度的荧光偏振测量表明,局部麻醉药使膜脂流动性略有增加。低剂量刀豆球蛋白A对转化细胞的自发凝集作用受到秋水仙碱和长春碱的抑制,但这些生物碱对经麻醉处理细胞的刀豆球蛋白A凝集作用没有影响。有证据表明,局部麻醉药可能会损害对秋水仙碱敏感的膜周边蛋白(微管)和对细胞松弛素B敏感的膜周边蛋白(微丝)。用秋水仙碱和细胞松弛素B联合处理未转化的3T3细胞,模拟了局部麻醉药增强对低剂量刀豆球蛋白A凝集作用敏感性的效果。本文提出了一个关于秋水仙碱敏感和细胞松弛素B敏感的周边膜蛋白在控制细胞表面凝集素受体拓扑分布中各自作用的假说。