Nicolson G L
J Supramol Struct. 1976;5(1):65-72. doi: 10.1002/jss.400050107.
Tertiary amine local anesthetics (dibucaine, tetracaine, procaine, etc.) modify cell morphology, concanavalin A (Con A)-mediated agglutinability and redistribution of Con A receptors. Con A agglutination of untransformed mouse 3T3 cells was enhanced at low concentrations of local anesthetics, and the dynamics of fluorescent-Con A indicated that ligand-induced clustering was increased in the presence of the drugs. In contast, these drugs inhibited Con A-induced receptor capping on mouse spleen cells. These effects can be duplicated by combinations of vinblastine (or colchicine) and cytochalasin B suggesting that local anesthetics act on microtubule and microfilament assemblies which are involved in the trans-membrane control of cell surface receptor mobility and distribution. It is proposed that tertiary amine local anesthetics displace plasma membrane-bound Ca2+, resulting in disengagement of microfilament systems from the plasma membrane and increased cellular Ca2+ concentration to levels which disrupt microtubular organization. The possible involvement of cellular Ca2+ in cytoskeletal destruction by local anesthetics was investigated utilizing Ca2+-specific ionophores A23187 and X537A. In media containing Ca2+ and cytochalasin B these ionophores caused effects similar to tertiary amine local anesthetics.
叔胺类局部麻醉药（丁卡因、丁哌卡因、普鲁卡因等）可改变细胞形态、伴刀豆球蛋白A（Con A）介导的凝集性以及Con A受体的再分布。在低浓度局部麻醉药作用下，未转化的小鼠3T3细胞的Con A凝集作用增强，荧光Con A的动力学表明在药物存在时配体诱导的聚集增加。相比之下，这些药物抑制Con A诱导的小鼠脾细胞上的受体帽形成。长春碱（或秋水仙碱）与细胞松弛素B的组合可产生类似效果，这表明局部麻醉药作用于参与细胞表面受体流动性和分布跨膜控制的微管和微丝组件。有人提出叔胺类局部麻醉药可置换质膜结合的Ca2+，导致微丝系统与质膜分离，并使细胞内Ca2+浓度升高至破坏微管组织的水平。利用Ca2+特异性离子载体A23187和X537A研究了细胞内Ca2+在局部麻醉药引起的细胞骨架破坏中的可能作用。在含有Ca2+和细胞松弛素B的培养基中，这些离子载体产生了与叔胺类局部麻醉药类似的效果。
