Nishiguchi E, Hamada N, Shindo J
Department of Dental Hygiene, Shonan Junior College, Kanagawa, Japan.
Eur J Pharmacol. 1995 Nov 3;286(1):1-8. doi: 10.1016/0014-2999(95)00427-m.
The mechanism of action of lidocaine, which is commonly used clinically as a local anesthetic, was studied in human red blood cells. The influx of [14C]lidocaine through the cell membrane induced reversible transformation of human red blood cells from discocytes to stomatocytes. This change in shape depended on the lidocaine concentration and required both ATP and carbonic anhydrase. The lidocaine-induced shape change occurred as a result of spectrin aggregation, which altered the intracellular environment of the human red blood cells, mediated by carbonic anhydrase and activation of vacuolar type H(+)-ATPase (V-ATPase). Lidocaine controlled the influx of 22Na into the human red blood cells in a concentration-dependent manner. When incubated in media containing 6-chloro-9-[(4-diethylamino)-1-methyl-butyl]amino-2-methoxyacridine (mepacrine), an inhibitor of Na+ channels, human red blood cells changed shape from discocytes to stomatocytes and the intracellular pH decreased. This phenomenon was very similar to the shape change induced by lidocaine. These results suggest that the mode of action of lidocaine is related to a conformational change in the cytoskeletal protein network.
利多卡因是临床常用的局部麻醉药，其作用机制在人类红细胞中进行了研究。[14C]利多卡因通过细胞膜的内流诱导人类红细胞从双凹圆盘状可逆转变为口形细胞。这种形状变化取决于利多卡因浓度，且需要ATP和碳酸酐酶。利多卡因诱导的形状变化是由于血影蛋白聚集导致的，这改变了人类红细胞的细胞内环境，由碳酸酐酶和液泡型H(+)-ATP酶（V-ATPase）的激活介导。利多卡因以浓度依赖的方式控制22Na流入人类红细胞。当在含有6-氯-9-[(4-二乙氨基)-1-甲基丁基]氨基-2-甲氧基吖啶（米帕林）（一种Na+通道抑制剂）的培养基中孵育时，人类红细胞从双凹圆盘状变为口形细胞，细胞内pH值降低。这种现象与利多卡因诱导的形状变化非常相似。这些结果表明，利多卡因的作用方式与细胞骨架蛋白网络的构象变化有关。
