title: Hypnotic effect of volatile anesthetics is mediated by PKC-γ dynamics.
abstract: BACKGROUND
  Although protein kinase C-γ (PKC-γ) is a target for the effects of volatile anesthetics, the molecular mechanisms of the kinase function remain unclear. We examined the effects of different types of anesthetics on PKC-γ knockout mice, and investigated the dynamics of the kinase in mouse brain.
  
  
  METHODS
  We measured the required number of times for loss of righting reflex (rtfLORR) after administration of isoflurane, sevoflurane, and propofol on PKC-γ knockout mice and compared with those of wild-type mice. We also used immunoblotting to investigate the intracellular distribution of PKC-γ and phosphorylated PKC-γ (p-PKC-γ) in brain of wild-type mice anesthetized by these anesthetics.
  
  
  RESULTS
  Isoflurane and sevoflurane significantly prolonged the rtfLORRs in PKC-γ knockout mice compared with those in wild-type mice, while no significant difference was observed between knockout and wild-type mice treated with propofol. Examination of the cellular fractions showed that PKC-γ was significantly decreased, whereas p-PKC-γ was significantly increased in the synaptic membrane fraction (P2). There was no significant change in the supernatant fraction (S). In propofol-treated mice, PKC-γ and p-PKC-γ showed no significant changes in P2 or S.
  
  
  CONCLUSIONS
  Our results provide new evidence to support the possibility of the involvement of PKC-γ in the actions of volatile anesthetics.
authors.affiliation: Department of Anesthesiology, Tokyo Medical University Hospital, Shinjuku-ku, Tokyo, Japan. a-takeda@tokyo-med.ac.jp
authors.forename: Akiko
authors.initials: A
authors.lastname: Takeda
authors.forename: Ayano
authors.initials: A
authors.lastname: Okita
authors.forename: Kouki
authors.initials: K
authors.lastname: Kaneko
authors.forename: Takeo
authors.initials: T
authors.lastname: Nagura
authors.forename: Naoto
authors.initials: N
authors.lastname: Iwase
authors.forename: Shusuke
authors.initials: S
authors.lastname: Sekine
authors.forename: Takayasu
authors.initials: T
authors.lastname: Kakinuma
authors.forename: Masashi
authors.initials: M
authors.lastname: Noguchi
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Hatakeyama
mesh_terms: D018685:Anesthetics, Inhalation / Q000008:administration & dosage*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010766:Phosphorylation / Q000187:drug effects / Q000235:genetics; D011493:Protein Kinase C / Q000172:deficiency; D057897:Reflex, Righting / Q000187:drug effects* / Q000235:genetics; D013997:Time Factors
chemical_list: D018685:Anesthetics, Inhalation; C087857:protein kinase C gamma; D011493:Protein Kinase C