Wafford K A, Whiting P J
Merck, Sharp and Dohme Research Laboratories, Harlow, Essex, UK.
FEBS Lett. 1992 Nov 23;313(2):113-7. doi: 10.1016/0014-5793(92)81424-k.
The mammalian GABAA receptor is a multisubunit protein containing a variety of binding sites for psychotropic agents. One of the most widely used of these drugs, ethanol, enhances the function of GABAA receptors in certain circumstances but not others. Previous studies have demonstrated that alternative splicing of the gamma 2L GABA subunit results in an ethanol sensitive and an ethanol-insensitive form, when combined with alpha and beta subunits. We have used in vitro mutagenesis and expression in Xenopus oocytes to show that the consensus site for phosphorylation by protein kinase C contained in the gamma 2L insert is critical for modulation by ethanol but not benzodiazepines, and manipulation of the phosphorylating enzymes in oocytes containing alpha 1 beta 1 gamma 2L can prevent ethanol enhancement. It is likely that phosphorylation or dephosphorylation of a specific site on the GABAA receptor protein can act as a control mechanism for neuronal responses to alcohol exposure.
哺乳动物γ-氨基丁酸A型（GABAA）受体是一种多亚基蛋白，含有多种精神药物结合位点。其中使用最广泛的药物之一乙醇，在某些情况下可增强GABAA受体的功能，但在其他情况下则不然。先前的研究表明，γ2L GABA亚基的可变剪接与α和β亚基结合时会产生乙醇敏感型和乙醇不敏感型。我们利用体外诱变和非洲爪蟾卵母细胞表达技术表明，γ2L插入片段中包含的蛋白激酶C磷酸化共有位点对乙醇调节至关重要，但对苯二氮䓬类药物调节不重要，并且在含有α1β1γ2L的卵母细胞中操纵磷酸化酶可阻止乙醇增强作用。GABAA受体蛋白上特定位点的磷酸化或去磷酸化很可能作为神经元对酒精暴露反应的一种控制机制。
