Ferguson R M, Schmidtke J R, Simmons R L
J Immunol. 1976 Mar;116(3):627-34.
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.
将氯丙嗪（CPZ）和利多卡因添加到由刀豆球蛋白A（Con A）、植物血凝素（PHA）、商陆有丝分裂原（PWM）和脂多糖（LPS）刺激的小鼠脾细胞培养物中。浓度大于5×10⁻⁶M的CPZ和浓度大于2×10⁻³M的利多卡因完全抑制了对所有四种有丝分裂原的促有丝分裂反应。通过台盼蓝摄取或⁵¹Cr释放测定，两种药物的最小抑制浓度均未干扰细胞活力。从培养物中去除药物后，这些作用完全逆转。在有丝分裂原暴露后间隔添加药物表明，抑制事件在暴露于有丝分裂原后相对较快发生。例如，在Con A刺激后24小时以上添加利多卡因或CPZ对氚标记胸腺嘧啶核苷掺入没有影响。环磷酸腺苷、环磷酸鸟苷（或其衍生物）或钙浓度的升高以及这些药物已知的膜活性作用和效应的快速可逆性有力地支持了局部麻醉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未受抑制。存在CPZ和利多卡因使细胞膜紊乱从而干扰第二信使的表面膜形成或作用或干扰细胞间相互作用的可能性。
