TY - JOUR T1 - Propofol Anesthesia Is Reduced in Phospholipase C–Related Inactive Protein Type-1 Knockout Mice JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 367 LP - 374 DO - 10.1124/jpet.116.239145 VL - 361 IS - 3 AU - Yoshikazu Nikaido AU - Tomonori Furukawa AU - Shuji Shimoyama AU - Junko Yamada AU - Keisuke Migita AU - Kohei Koga AU - Tetsuya Kushikata AU - Kazuyoshi Hirota AU - Takashi Kanematsu AU - Masato Hirata AU - Shinya Ueno Y1 - 2017/06/01 UR - http://jpet.aspetjournals.org/content/361/3/367.abstract N2 - The GABA type A receptor (GABAA-R) is a major target of intravenous anesthetics. Phospholipase C–related inactive protein type-1 (PRIP-1) is important in GABAA-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 (PRIP-1 KO) 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 PRIP-1 KO mice. OA injection enhanced phosphorylation of cortical the GABAA-R β3 subunit in PRIP-1 KO mice. These results suggest that PRIP-1–mediated GABAA-R β3 subunit phosphorylation might be involved in the general anesthetic action induced by propofol but not by etomidate or pentobarbital. ER -