Propofol Anesthesia Is Reduced in Phospholipase C-Related Inactive Protein Type-1 Knockout Mice

The GABA type A receptor (GABA -R) is a major target of intravenous anesthetics. Phospholipase C-related inactive protein type-1 (PRIP-1) is important in GABA -R phosphorylation and membrane trafficking. In this study, we investigated the role of PRIP-1 in general anesthetic action. The anesthetic e...

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Bibliographic Details
Published in:The Journal of pharmacology and experimental therapeutics 2017-06, Vol.361 (3), p.367-374
Main Authors: Nikaido, Yoshikazu, Furukawa, Tomonori, Shimoyama, Shuji, Yamada, Junko, Migita, Keisuke, Koga, Kohei, Kushikata, Tetsuya, Hirota, Kazuyoshi, Kanematsu, Takashi, Hirata, Masato, Ueno, Shinya
Format: Article
Language:English
Subjects:
Adaptor Proteins, Signal Transducing - deficiency
Anesthetics, Intravenous - administration & dosage
Animals
Dose-Response Relationship, Drug
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Propofol - administration & dosage
Reaction Time - drug effects
Reaction Time - physiology
Receptors, GABA-A - metabolism
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Summary:The GABA type A receptor (GABA -R) is a major target of intravenous anesthetics. Phospholipase C-related inactive protein type-1 (PRIP-1) is important in GABA -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 ( ) 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 mice. OA injection enhanced phosphorylation of cortical the GABA -R 3 subunit in mice. These results suggest that PRIP-1-mediated GABA -R 3 subunit phosphorylation might be involved in the general anesthetic action induced by propofol but not by etomidate or pentobarbital.
ISSN:0022-3565
1521-0103
DOI:10.1124/jpet.116.239145