1型磷脂酶C相关无活性蛋白基因敲除小鼠的丙泊酚麻醉作用减弱。
Propofol Anesthesia Is Reduced in Phospholipase C-Related Inactive Protein Type-1 Knockout Mice.
作者信息
Nikaido Yoshikazu, Furukawa Tomonori, Shimoyama Shuji, Yamada Junko, Migita Keisuke, Koga Kohei, Kushikata Tetsuya, Hirota Kazuyoshi, Kanematsu Takashi, Hirata Masato, Ueno Shinya
机构信息
Graduate School of Medicine (Y.N.), Department of Neurophysiology (Y.N., T.F., K.K., S.U.) and Department of Anesthesiology, Graduate School of Medicine (Y.N., T.Ku., K.H.), Research Center for Child Mental Development, Graduate School of Medicine (S.S., S.U.), and Department of Biomedical Sciences, Division of Medical Life Sciences, Graduate School of Health Sciences (J.Y.), Hirosaki University, Hirosaki, Japan; Department of Drug Informatics, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan (K.M.); Department of Cellular and Molecular Pharmacology, Division of Basic Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan (T.Ka.); Laboratory of Molecular and Cellular Biochemistry, Faculty of Dental Science, Kyushu University, Fukuoka, Japan (M.H.); Fukuoka Dental College, Fukuoka, Japan (M.H.).
Graduate School of Medicine (Y.N.), Department of Neurophysiology (Y.N., T.F., K.K., S.U.) and Department of Anesthesiology, Graduate School of Medicine (Y.N., T.Ku., K.H.), Research Center for Child Mental Development, Graduate School of Medicine (S.S., S.U.), and Department of Biomedical Sciences, Division of Medical Life Sciences, Graduate School of Health Sciences (J.Y.), Hirosaki University, Hirosaki, Japan; Department of Drug Informatics, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan (K.M.); Department of Cellular and Molecular Pharmacology, Division of Basic Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan (T.Ka.); Laboratory of Molecular and Cellular Biochemistry, Faculty of Dental Science, Kyushu University, Fukuoka, Japan (M.H.); Fukuoka Dental College, Fukuoka, Japan (M.H.)
出版信息
J Pharmacol Exp Ther. 2017 Jun;361(3):367-374. doi: 10.1124/jpet.116.239145. Epub 2017 Apr 12.
The GABA type A receptor (GABA-R) is a major target of intravenous anesthetics. Phospholipase C-related inactive protein type-1 (PRIP-1) is important in GABA-R phosphorylation and membrane trafficking. In this study, we investigated the role of PRIP-1 in general anesthetic action. The anesthetic effects of propofol, etomidate, and pentobarbital were evaluated in wild-type and PRIP-1 knockout () mice by measuring the latency and duration of loss of righting reflex (LORR) and loss of tail-pinch withdrawal response (LTWR). The effect of pretreatment with okadaic acid (OA), a protein phosphatase 1/2A inhibitor, on propofol- and etomidate-induced LORR was also examined. PRIP-1 deficiency provided the reduction of LORR and LTWR induced by propofol but not by etomidate or pentobarbital, indicating that PRIP-1 could determine the potency of the anesthetic action of propofol. Pretreatment with OA recovered the anesthetic potency induced by propofol in mice. OA injection enhanced phosphorylation of cortical the GABA-R 3 subunit in mice. These results suggest that PRIP-1-mediated GABA-R 3 subunit phosphorylation might be involved in the general anesthetic action induced by propofol but not by etomidate or pentobarbital.
γ-氨基丁酸A型受体（GABA-R）是静脉麻醉药的主要作用靶点。1型磷脂酶C相关失活蛋白（PRIP-1）在GABA-R磷酸化和膜转运过程中发挥重要作用。在本研究中，我们探究了PRIP-1在全身麻醉作用中的角色。通过测量翻正反射消失（LORR）和夹尾退缩反应消失（LTWR）的潜伏期和持续时间，评估了野生型和PRIP-1基因敲除（）小鼠对丙泊酚、依托咪酯和戊巴比妥的麻醉效果。还检测了蛋白磷酸酶1/2A抑制剂冈田酸（OA）预处理对丙泊酚和依托咪酯诱导的LORR的影响。PRIP-1缺陷使丙泊酚诱导的LORR和LTWR降低，但依托咪酯或戊巴比妥诱导的未降低，这表明PRIP-1可决定丙泊酚麻醉作用的效能。OA预处理恢复了基因敲除小鼠中丙泊酚诱导的麻醉效能。OA注射增强了基因敲除小鼠皮质GABA-R 3亚基的磷酸化。这些结果提示，PRIP-1介导的GABA-R 3亚基磷酸化可能参与丙泊酚诱导的全身麻醉作用，而不参与依托咪酯或戊巴比妥诱导的全身麻醉作用。
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