title: Propofol Anesthesia Is Reduced in Phospholipase C-Related Inactive Protein Type-1 Knockout Mice.
abstract: 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 inPRIP-1 KOmice. OA injection enhanced phosphorylation of cortical the GABAA-Rβ3 subunit inPRIP-1 KOmice. These results suggest that PRIP-1-mediated GABAA-Rβ3 subunit phosphorylation might be involved in the general anesthetic action induced by propofol but not by etomidate or pentobarbital.
authors.affiliation: 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.).
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Nikaido
authors.affiliation: 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.).
authors.forename: Tomonori
authors.initials: T
authors.lastname: Furukawa
authors.affiliation: 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.).
authors.forename: Shuji
authors.initials: S
authors.lastname: Shimoyama
authors.affiliation: 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.).
authors.forename: Junko
authors.initials: J
authors.lastname: Yamada
authors.affiliation: 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.).
authors.forename: Keisuke
authors.initials: K
authors.lastname: Migita
authors.affiliation: 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.).
authors.forename: Kohei
authors.initials: K
authors.lastname: Koga
authors.affiliation: 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.).
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kushikata
authors.affiliation: 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.).
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Hirota
authors.affiliation: 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.).
authors.forename: Takashi
authors.initials: T
authors.lastname: Kanematsu
authors.affiliation: 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.).
authors.forename: Masato
authors.initials: M
authors.lastname: Hirata
authors.affiliation: 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.) shinyau@hirosaki-u.ac.jp.
authors.forename: Shinya
authors.initials: S
authors.lastname: Ueno
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency*; D018686:Anesthetics, Intravenous / Q000008:administration & dosage*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015742:Propofol / Q000008:administration & dosage*; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D011963:Receptors, GABA-A / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018686:Anesthetics, Intravenous; C496391:Plcl1 protein, mouse; D011963:Receptors, GABA-A; D015742:Propofol