Raz A, Goldman R
Biochim Biophys Acta. 1976 Nov 11;455(1):226-40. doi: 10.1016/0005-2736(76)90166-8.
The extensive vacuolation elecited in mouse peritoneal macrophages in response to interaction with concanavalin A is markedly enhanced by a simultaneous exposure to anaesthetics. The potency of enchancing vacuolation increases within the series of normal alcohols with chain length C10 greater than C8 greater than C7 greater than C6. From the four tertiary amine local anaesthetics tested lidocaine and procaine are by far more effective than tetracaine and dibucaine. The latter two induce extensive cell shrinkage at concentrations at which the first two exhibit optimum enhancing capacity. Of the tested compounds chlorpromazine has the highest membrane/buffer partition coefficient and it exhibits its optimum enhancing effect on concanavalin A-induced macrophage vacuolation at the lowest drug concentration. The binding of [3H] concanavalin A as well as its internalization by macrophages incubated with the lectin for 15, 45 and 90 min are not affected significantly in the presence of decanol, procaine or chlorpromazine at concentrations of maximum enhancing effect on vacuolation. Thus enhancement of vacuolation does not stem from an increase in the rate or extent of concanavalin A interiorization. The rate at which vacuoles are generated is however markedly increased in the presence of chlorpromazine and the resulting vacuoles are of a larger diameter. At 2-5 fold the concentration required for inhibition of maximum enhancing effect, the drugs lead to extensive macrophage shrinkage and to depletion of intracellular ATP. Phagocytosis of heat-killed yeast cells is reduced by tertiary amine anaesthetics at concentrations optimal for enhancement of concanavalin A-induced vacuolation. Enhanced intracellular fusion of concanavalin A-bearing pinosomes to form vacuoles is discussed in terms of current ideas on factors vacuoles is discussed in terms of current ideas on factors vacuoles is discussed in terms of current ideas on factors affecting membrane fusion and the effects of anaesthetics on membrane organization of lipids, intramembraneous particles, glycoprotein receptors and the possible control by cytoskeletal elements. The results best fit the hypothesis that enhanced fusion correlates with membrane aggregation of both intramembraneous particles and concanavalin A receptor and the formation of areas relatively deplete of these structures and enriched in phospholipids.
与伴刀豆球蛋白A相互作用后，小鼠腹腔巨噬细胞中出现的广泛空泡化，在同时暴露于麻醉剂时会显著增强。在碳链长度为C10大于C8大于C7大于C6的一系列正醇中，增强空泡化的效力会增加。在所测试的四种叔胺局部麻醉剂中，利多卡因和普鲁卡因远比丁卡因和布比卡因有效。后两者在浓度达到前两者表现出最佳增强能力时，会诱导细胞大量收缩。在所测试的化合物中，氯丙嗪具有最高的膜/缓冲液分配系数，并且在最低药物浓度下对伴刀豆球蛋白A诱导的巨噬细胞空泡化表现出最佳增强作用。在对空泡化具有最大增强作用的浓度下，存在癸醇、普鲁卡因或氯丙嗪时，[3H]伴刀豆球蛋白A的结合及其被与凝集素孵育15、45和90分钟的巨噬细胞内化的过程均未受到显著影响。因此，空泡化的增强并非源于伴刀豆球蛋白A内化速率或程度的增加。然而，在氯丙嗪存在的情况下，空泡产生的速率显著增加，并且产生的空泡直径更大。在抑制最大增强作用所需浓度的2 - 5倍时，这些药物会导致巨噬细胞大量收缩并消耗细胞内ATP。在对伴刀豆球蛋白A诱导的空泡化增强最适宜的浓度下，叔胺类麻醉剂会降低热杀死酵母细胞的吞噬作用。关于伴刀豆球蛋白A携带的胞饮小体增强细胞内融合形成空泡的现象，根据当前关于影响膜融合的因素以及麻醉剂对脂质膜组织、膜内颗粒、糖蛋白受体的影响以及细胞骨架成分可能的控制等观点进行了讨论。这些结果最符合这样的假设，即增强的融合与膜内颗粒和伴刀豆球蛋白A受体的膜聚集以及这些结构相对缺乏且富含磷脂的区域的形成相关。
