Ueda I, Kamaya H, Eyring H
Proc Natl Acad Sci U S A. 1976 Feb;73(2):481-5. doi: 10.1073/pnas.73.2.481.
The kinetics of the action of local anesthetics upon firefly luciferin and luciferase systems is presented. Clinical concentrations of local anesthetics inhibited this ATP-induced luminescence in a dose-dependent manner. From the effects of temperature and pH upon the inhibitory action of the local anesthetics, it is concluded that hydrophobic ligand-enzyme interaction is the predominant cause of the inhibition, but hydrophilic interaction also contributes to the inhibition to a lesser degree. A molecular theory of anesthesia is outlined which postulates that release of electrostricted water molecules from the hydrophilic parts of the enzyme due to the protein conformational changes induced by anesthetics is the cause of the decreased luminescence. A similar mechanism is expected to occur at the cell membrane, which probably dehydrates the sodium channel and suppresses the conductance of this ion across the membrane. These events lead to a volume expansion of the total system, and the system becomes reactive to a pressure which reverses the anesthesia by shifting the equilibrium to the nonanesthetized original volume. The pressure antagonism of anesthesia can be explained by this overall volume expansion and not by a mere swelling of the cell membrane.
本文介绍了局部麻醉药对萤火虫荧光素和荧光素酶系统作用的动力学。局部麻醉药的临床浓度以剂量依赖的方式抑制这种由ATP诱导的发光。从温度和pH值对局部麻醉药抑制作用的影响可以得出结论，疏水配体-酶相互作用是抑制的主要原因，但亲水相互作用在较小程度上也对抑制有贡献。概述了一种麻醉分子理论，该理论假定由于麻醉药诱导的蛋白质构象变化，从酶的亲水部分释放出电收缩水分子是发光降低的原因。预计在细胞膜上会发生类似的机制，细胞膜可能会使钠通道脱水并抑制该离子跨膜的电导。这些事件导致整个系统的体积膨胀，并且该系统对压力产生反应，通过将平衡转移到未麻醉的原始体积来逆转麻醉。麻醉的压力拮抗作用可以用这种整体体积膨胀来解释，而不仅仅是细胞膜的肿胀。
