PMID- 21389746 OWN - NLM STAT- MEDLINE DCOM- 20110805 LR - 20110419 IS - 1423-0313 (Electronic) IS - 0031-7012 (Linking) VI - 87 IP - 3-4 DP - 2011 TI - Effects of different types of anesthetic agents on cellular protein kinase C-gamma dynamics in mouse brain. PG - 180-6 LID - 10.1159/000324317 [doi] AB - BACKGROUND/AIMS: Although protein kinase C-gamma (PKC-gamma) is a target for the effects of volatile anesthetics, the molecular mechanisms of the kinase function during their action remain unclear. We examined the effects of different types of anesthetics on PKC-gamma knockout mice. Furthermore, we investigated the dynamics of the kinase in brain cells obtained from mice anesthetized with these anesthetics. METHODS: We measured the required times for loss of righting reflex (rtfLORR) after administration of isoflurane, sevoflurane, or propofol on PKC-gamma knockout mice and compared the times with those of wild-type mice. We also used immunoblotting to investigate the intracellular distribution of PKC-gamma and phosphorylated PKC-gamma (p-PKC-gamma) in brain cell fractions obtained from wild-type mice during the loss of righting reflex induced by these anesthetics. RESULTS: Isoflurane (2.6%) and sevoflurane (3.4%) used at twice the minimum alveolar concentration significantly prolonged the rtfLORRs in PKC-gamma knockout mice compared to those in wild-type mice. On the other hand, no significant difference was observed between knockout and wild-type mice treated with propofol (200 mg/kg). Examination of the cellular fractions isolated from volatile anesthetic-treated mouse brains showed that PKC-gamma was significantly decreased in the synaptic membrane fraction (P2), whereas p-PKC-gamma was significantly increased in P2. There was no significant change in the supernatant fraction (S). In propofol-treated mice, PKC-gamma and p-PKC-gamma showed no significant changes in P2 or S. CONCLUSION: Our results provide new evidence to support the possibility of the involvement of PKC-gamma in the actions of volatile anesthetics. CI - Copyright (c) 2011 S. Karger AG, Basel. FAU - Takeda, Akiko AU - Takeda A AD - Department of Anesthesiology, Tokyo Medical University Hospital, Tokyo, Japan. a-takeda @ tokyo-med.ac.jp FAU - Miyashita, Ryoichi AU - Miyashita R FAU - Nagura, Takeo AU - Nagura T FAU - Sekine, Shusuke AU - Sekine S FAU - Murozono, Michihiro AU - Murozono M FAU - Matsumoto, Shohei AU - Matsumoto S FAU - Uchino, Hiroyuki AU - Uchino H LA - eng PT - Journal Article DEP - 20110310 PL - Switzerland TA - Pharmacology JT - Pharmacology JID - 0152016 RN - 0 (Anesthetics, Inhalation) RN - 0 (Anesthetics, Intravenous) RN - EC 2.7.1.- (protein kinase C gamma) RN - EC 2.7.11.13 (Protein Kinase C) SB - IM MH - Anesthetics, Inhalation/administration & dosage/*pharmacology MH - Anesthetics, Intravenous/administration & dosage/*pharmacology MH - Animals MH - Blotting, Western MH - Brain/*drug effects/enzymology MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Phosphorylation MH - Protein Kinase C/genetics/*metabolism/physiology MH - Subcellular Fractions/drug effects/enzymology EDAT- 2011/03/11 06:00 MHDA- 2011/08/06 06:00 CRDT- 2011/03/11 06:00 PHST- 2010/12/21 00:00 [received] PHST- 2011/01/12 00:00 [accepted] PHST- 2011/03/11 06:00 [entrez] PHST- 2011/03/11 06:00 [pubmed] PHST- 2011/08/06 06:00 [medline] AID - 000324317 [pii] AID - 10.1159/000324317 [doi] PST - ppublish SO - Pharmacology. 2011;87(3-4):180-6. doi: 10.1159/000324317. Epub 2011 Mar 10.