General anesthetic actions on GABA A receptors in vivo are reduced in phospholipase C-related catalytically inactive protein knockout mice

Masaki Hayashiuchi, Tomoya Kitayama, Katsuya Morita, Yosuke Yamawaki, Kana Oue, Taiga Yoshinaka, Satoshi Asano, Kae Harada, Youngnam Kang, Masato Hirata, Masahiro Irifune, Mitsugi Okada, Takashi Kanematsu

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Purpose: The aim of this study was to investigate the action of general anesthetics in phospholipase C-related catalytically inactive protein (PRIP)-knockout (KO) mice that alter GABA A receptor signaling. Methods: PRIP regulates the intracellular trafficking of β subunit-containing GABA A receptors in vitro. In this study, we examined the effects of intravenous anesthetics, propofol and etomidate that act via β subunit-containing GABA A receptors, in wild-type and Prip-KO mice. Mice were intraperitoneally injected with a drug, and a loss of righting reflex (LORR) assay and an electroencephalogram analysis were performed. Results: The cell surface expression of GABA A receptor β3 subunit detected by immunoblotting was decreased in Prip-knockout brain compared with that in wild-type brain without changing the expression of other GABA A receptor subunits. Propofol-treated Prip-KO mice exhibited significantly shorter duration of LORR and had lower total anesthetic score than wild-type mice in the LORR assay. The average duration of sleep time in an electroencephalogram analysis was shorter in propofol-treated Prip-KO mice than in wild-type mice. The hypnotic action of etomidate was also reduced in Prip-KO mice. However, ketamine, an NMDA receptor antagonist, had similar effects in the two genotypes. Conclusion: PRIP regulates the cell surface expression of the GABA A receptor β3 subunit and modulates general anesthetic action in vivo. Elucidation of the involved regulatory mechanisms of GABA A receptor-dependent signaling would inform the development of safer anesthetic therapies for clinical applications.

Original languageEnglish
Pages (from-to)531-538
Number of pages8
JournalJournal of Anesthesia
Volume31
Issue number4
DOIs
Publication statusPublished - Aug 1 2017
Externally publishedYes

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General Anesthetics
Type C Phospholipases
GABA-A Receptors
Knockout Mice
Righting Reflex
Propofol
Proteins
Etomidate
Anesthetics
Electroencephalography
Intravenous Anesthetics
Brain
Ketamine
N-Methyl-D-Aspartate Receptors
Hypnotics and Sedatives
Immunoblotting
Sleep
Membrane Proteins
Genotype
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Anesthesiology and Pain Medicine

Cite this

General anesthetic actions on GABA A receptors in vivo are reduced in phospholipase C-related catalytically inactive protein knockout mice . / Hayashiuchi, Masaki; Kitayama, Tomoya; Morita, Katsuya; Yamawaki, Yosuke; Oue, Kana; Yoshinaka, Taiga; Asano, Satoshi; Harada, Kae; Kang, Youngnam; Hirata, Masato; Irifune, Masahiro; Okada, Mitsugi; Kanematsu, Takashi.

In: Journal of Anesthesia, Vol. 31, No. 4, 01.08.2017, p. 531-538.

Research output: Contribution to journalArticle

Hayashiuchi, M, Kitayama, T, Morita, K, Yamawaki, Y, Oue, K, Yoshinaka, T, Asano, S, Harada, K, Kang, Y, Hirata, M, Irifune, M, Okada, M & Kanematsu, T 2017, ' General anesthetic actions on GABA A receptors in vivo are reduced in phospholipase C-related catalytically inactive protein knockout mice ', Journal of Anesthesia, vol. 31, no. 4, pp. 531-538. https://doi.org/10.1007/s00540-017-2350-2
Hayashiuchi, Masaki ; Kitayama, Tomoya ; Morita, Katsuya ; Yamawaki, Yosuke ; Oue, Kana ; Yoshinaka, Taiga ; Asano, Satoshi ; Harada, Kae ; Kang, Youngnam ; Hirata, Masato ; Irifune, Masahiro ; Okada, Mitsugi ; Kanematsu, Takashi. / General anesthetic actions on GABA A receptors in vivo are reduced in phospholipase C-related catalytically inactive protein knockout mice In: Journal of Anesthesia. 2017 ; Vol. 31, No. 4. pp. 531-538.
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AU - Kitayama, Tomoya

AU - Morita, Katsuya

AU - Yamawaki, Yosuke

AU - Oue, Kana

AU - Yoshinaka, Taiga

AU - Asano, Satoshi

AU - Harada, Kae

AU - Kang, Youngnam

AU - Hirata, Masato

AU - Irifune, Masahiro

AU - Okada, Mitsugi

AU - Kanematsu, Takashi

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