Evers A S, Berkowitz B A, d'Avignon D A
Nature. 1987;328(6126):157-60. doi: 10.1038/328157a0.
Two theories of the molecular mechanism of volatile anaesthetic action suggest either that anaesthetics cause a generalized perturbation of neuronal membrane structure, probably through a nonspecific interaction with membrane lipids, or that anaesthetics bind to sets of sites of appropriate molecular dimension on membrane proteins. Based on the recent finding that fluorinated anaesthetics can be observed in animal tissue by 19F nuclear magnetic resonance (19F-NMR) spectroscopy, we have used 19F-NMR to quantify the interaction between the volatile anaesthetic halothane and rat brain tissue. Steady-state brain halothane concentration was found to be a non-linear function of inspired concentration, with apparent saturation of brain occurring at inspired halothane concentrations above 2.5% by volume. Using a spin-echo pulse sequence it was found that halothane exists in two distinct chemical environments in brain, characterized by different spin-spin relaxation times (T2), chemical shifts and kinetics of occupancy. Halothane concentration in one of these environments (T2 = 3.6 ms) was saturated at approximately 2.5% inspired halothane; occupancy of this environment was found to correlate with the anaesthetic effect of the drug. In the other environment (T2 = 43 ms), brain halothane concentration was a linear function of inspired concentration. These data suggest the existence of a saturable anaesthetic site for halothane in brain and do not support the concept that anaesthetics act by nonspecific membrane perturbation.
关于挥发性麻醉剂作用分子机制的两种理论表明，麻醉剂要么通过与膜脂的非特异性相互作用，引起神经元膜结构的普遍扰动，要么与膜蛋白上适当分子尺寸的位点结合。基于最近通过19F核磁共振（19F-NMR）光谱在动物组织中观察到氟化麻醉剂这一发现，我们使用19F-NMR来量化挥发性麻醉剂氟烷与大鼠脑组织之间的相互作用。发现稳态脑氟烷浓度是吸入浓度的非线性函数，当吸入氟烷浓度高于2.5%（体积）时，脑内出现明显的饱和现象。使用自旋回波脉冲序列发现，氟烷在脑中存在两种不同的化学环境，其特征在于不同的自旋 - 自旋弛豫时间（T2）、化学位移和占据动力学。其中一种环境（T2 = 3.6毫秒）中的氟烷浓度在吸入氟烷约2.5%时达到饱和；发现该环境的占据情况与药物的麻醉效果相关。在另一种环境（T2 = 43毫秒）中，脑氟烷浓度是吸入浓度的线性函数。这些数据表明脑中存在氟烷的可饱和麻醉位点，并不支持麻醉剂通过非特异性膜扰动起作用的概念。
