Lam D W, Reynolds J N
Department of Pharmacology and Toxicology, Queen's University, Kingston, Ontario, Canada.
Brain Res. 1998 Feb 16;784(1-2):179-87. doi: 10.1016/s0006-8993(97)01334-6.
Propofol (2,6-diisopropylphenol) is an intravenous general anaesthetic which can directly activate and positively modulate the GABAA receptor. The effects of propofol on human recombinant GABAA receptors were studied in Xenopus oocytes expressing either alpha1beta2, alpha1beta2gamma2L, or alpha2beta2gamma2L receptor isoforms. In all receptor isoforms tested, propofol was able to potentiate the GABA-activated currents in a concentration-dependent manner. Although propofol potentiated both alpha1beta2 and alpha1beta2gamma2L receptor isoforms with equal affinity, the efficacy of propofol potentiation was markedly greater in the alpha1beta2 receptor isoform. In contrast, potentiation of the alpha2beta2gamma2L receptor isoform by propofol occurred with higher affinity and lower efficacy than in the alpha1beta2gamma2L receptor isoform. Propofol directly activated all three receptor isoforms in a concentration dependent manner. Addition of the gamma2L subunit subtype to the alpha1beta2 receptor isoform decreased receptor sensitivity to direct activation by propofol. Replacement of the alpha1-subunit subtype with the alpha2-subunit subtype increased receptor sensitivity to propofol's direct effects. These results suggest that the alpha-and gamma2L-subunit subtypes each have the ability to influence both the direct and modulatory actions of propofol on GABAA receptor function.
丙泊酚（2,6 - 二异丙基苯酚）是一种静脉全身麻醉剂，可直接激活并正向调节GABAA受体。在表达α1β2、α1β2γ2L或α2β2γ2L受体亚型的非洲爪蟾卵母细胞中研究了丙泊酚对人重组GABAA受体的影响。在所有测试的受体亚型中，丙泊酚能够以浓度依赖的方式增强GABA激活的电流。虽然丙泊酚以相同的亲和力增强α1β2和α1β2γ2L受体亚型，但丙泊酚增强的效力在α1β2受体亚型中明显更大。相比之下，丙泊酚对α2β2γ2L受体亚型的增强作用比在α1β2γ2L受体亚型中具有更高的亲和力和更低的效力。丙泊酚以浓度依赖的方式直接激活所有三种受体亚型。向α1β2受体亚型添加γ2L亚基亚型会降低受体对丙泊酚直接激活的敏感性。用α2亚基亚型替代α1亚基亚型会增加受体对丙泊酚直接作用的敏感性。这些结果表明，α和γ2L亚基亚型各自都有能力影响丙泊酚对GABAA受体功能的直接和调节作用。
