Inhibition of mitogen-induced lymphocyte transformation by local anesthetics.
Inhibition of mitogen-induced lymphocyte transformation by local anesthetics.
复制标题
局部麻醉剂抑制有丝分裂原诱导的淋巴细胞转化。
作者：
R. Ferguson;J. Schmidtke;R. Simmons
在concanvalin A （Con A）、植物血凝素（PHA）、美洲商陆丝裂原（PWM）和脂多糖（LPS）刺激的小鼠脾细胞培养中加入氯丙嗪（CPZ）和利多卡因。CPZ浓度大于5 × 10(-6)M和利多卡因浓度大于2 × 10(-3)M完全抑制对所有四种有丝分裂原的有丝分裂反应。通过台盼蓝摄取或51Cr释放测定，两种药物的最低抑制浓度均不干扰细胞活力。从培养物中去除药物后，效果完全逆转。在有丝分裂原暴露后每隔一段时间加入药物表明，抑制事件在暴露于有丝分裂原后相对较快地发生。例如，在Con A刺激后超过24小时加入利多卡因或CPZ对氚化胸苷的掺入没有影响。这些药物的环AMP、环GMP（或其衍生物）或钙素膜活性作用的浓度升高以及这种作用的快速可逆性有力地支持了局麻药作用于淋巴细胞表面膜的观点。在利多卡因或CPZ存在的情况下，放射性标记的Con A或LPS与淋巴细胞膜的结合不受抑制。CPZ和利多卡因可能扰乱细胞膜，从而干扰表面膜的加工或第二信使的作用，或干扰细胞间的相互作用。
Chlorpromazine (CPZ) and lidocaine were added to cultures of mouse spleen cells stimulated by concanvalin A (Con A), phytohemagglutinin (PHA), pokeweed mitogen (PWM) and lipopolysaccharide (LPS). Concentrations of CPZ greater than 5 x 10(-6)M and concentrations of lidocaine greater than 2 x 10(-3)M totally inhibited the mitogenic responses to all four mitogens. Minimal inhibitory concentrations of neither drug interferred with cell viability as determined by trypan blue uptake or 51Cr release. The effects were totally reversed by the removal of the drugs from the culture. Addition of the drug at intervals after mitogen exposure demonstrated that the inhibited event occurred relatively soon after exposure to the mitogen. For example, the addition of lidocaine or CPZ more than 24 hr after Con A stimulation had no effect on tritiated thymidine incorporation. Elevated concentrations of cyclic AMP, cyclic GMP (or their derivatives) or calciunown membrane active actions of these drugs and the rapid reversibility of the effect strongly support the idea that the local anesthetics act on the surface membrane of lymphocytes. Binding of radiolabeled Con A or LPS to lymphocyte membranes in the presence of lidocaine or CPZ was not inhibited. The possibility exists that CPZ and lidocaine disorganized cell membranes so as to interfere with the surface membrane elaboration or action of a second messenger, or interfere with cell-cell interactions.