Propofol anesthesia is reduced in phospholipase c-related inactive protein type-1 knockout mices

Yoshikazu Nikaido, Tomonori Furukawa, Shuji Shimoyama, Junko Yamada, Keisuke Migita, Kohei Koga, Tetsuya Kushikata, Kazuyoshi Hirota, Takashi Kanematsu, Masato Hirata, Shinya Ueno

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

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. Pre-treatment with OA recovered the anesthetic potency induced by propofol in PRIP-1 KO mice. OA injection enhanced phos-phorylation 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.

Original languageEnglish
Pages (from-to)367-374
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume361
Issue number3
DOIs
Publication statusPublished - Jun 1 2017
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

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