General anesthetic actions on GABAA receptors in vivo are reduced in phospholipase C-related catalytically inactive protein knockout mice
| Autor: | Kae Harada, Katsuya Morita, Tomoya Kitayama, Mitsugi Okada, Masato Hirata, Taiga Yoshinaka, Kana Oue, Masaki Hayashiuchi, Satoshi Asano, Youngnam Kang, Masahiro Irifune, Takashi Kanematsu, Yosuke Yamawaki |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Phospholipase C GABAA receptor business.industry Pharmacology GABAA-rho receptor 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Anesthesiology and Pain Medicine Endocrinology nervous system Etomidate Anesthesia Internal medicine Knockout mouse Anesthetic medicine NMDA receptor business Receptor 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Journal of Anesthesia. 31:531-538 |
| ISSN: | 1438-8359 0913-8668 |
| DOI: | 10.1007/s00540-017-2350-2 |
| Popis: | 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 GABAA receptor signaling. PRIP regulates the intracellular trafficking of β subunit-containing GABAA receptors in vitro. In this study, we examined the effects of intravenous anesthetics, propofol and etomidate that act via β subunit-containing GABAA 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. The cell surface expression of GABAA 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 GABAA 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. PRIP regulates the cell surface expression of the GABAA receptor β3 subunit and modulates general anesthetic action in vivo. Elucidation of the involved regulatory mechanisms of GABAA receptor-dependent signaling would inform the development of safer anesthetic therapies for clinical applications. |
| Databáze: | OpenAIRE |
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