DO GENERAL-ANESTHETICS ACT BY COMPETITIVE-BINDING TO SPECIFIC RECEPTORS
DO GENERAL-ANESTHETICS ACT BY COMPETITIVE-BINDING TO SPECIFIC RECEPTORS
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DOI：
10.1038/310599a0
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发表时间：
1984-01-01
期刊：
影响因子：
64.8
通讯作者：
LIEB, WR
中科院分区：
文献类型：
--
作者：
FRANKS, NP;LIEB, WR
大多数蛋白质在诱导全身麻醉的浓度下对麻醉剂的存在不敏感，而有些蛋白质被某些药物抑制，而不是其他药物1。在这里，我们表明，在100，000倍的效力范围内，纯可溶性蛋白质（萤火虫荧光素酶）的活性在麻醉剂浓度下可以被抑制50%，麻醉剂浓度基本上与麻醉动物的浓度相同。这一特性适用于吸入剂（如氟烷、甲氧氟烷和氯仿）、脂肪族和芳香族醇、酮、醚和烷烃。考虑到这种抑制在本质上是竞争性的，麻醉剂分子与底物（乙酰胆碱）分子竞争结合蛋白质，这一发现更加引人注目。我们发现，麻醉剂结合位点只能容纳一个大的，但不止一个小的，麻醉剂分子。我们的研究结果表明，显着的机制是，一般的麻醉剂，尽管其化学和结构的多样性，通过竞争与内源性配体结合到特定的受体。
Most proteins are insensitive to the presence of anaesthetics at concentrations which induce general anaesthesia, while some are inhibited by certain agents but not others1. Here we show that, over a 100,000-fold range of potencies, the activity of a pure soluble protein (firefly luciferase) can be inhibited by 50% at anaesthetic concentrations which are essentially identical to those which anaesthetize animals. This identity holds for inhalational agents (such as halothane, methoxyflurane and chloroform), aliphatic and aromatic alcohols, ketones, ethers and alkanes. This finding is all the more striking in view of the fact that the inhibition is shown to be competitive in nature, with anaesthetic molecules competing with substrate (luciferin) molecules for binding to the protein. We show that the anaesthetic-binding site can accommodate only one large, but more than one small, anaesthetic molecule. The obvious mechanism suggested by our results is that general anaesthetics, despite their chemical and structural diversity, act by competing with endogenous ligands for binding to specific receptors.