title: Anesthetics inhibit extracellular signal-regulated Kinase1/2 phosphorylation via NMDA receptor, phospholipase C and protein kinase C in mouse hippocampal slices.
abstract: Extracellular signal-regulated kinase 1/2 (ERK1/2) has been implicated in learning and memory; however, whether intravenous anesthetics modulate ERK1/2 remains unknown. The aim of this study was to examine the effect of several intravenous anesthetics on the phosphorylation of ERK1/2 in the hippocampus of adult mice.
  
  
  
  Western blotting was used to examine cellular levels of phosphorylated and unphosphorylated ERK1/2 in mouse hippocampus slices, which were incubated with or without anesthetics including propofol, etomidate, ketamine and midazolam, a protein kinase C (PKC) activator or inhibitor, or phospholipase C (PLC) activator or inhibitor.
  
  
  
  Propofol, etomidate, ketamine and midazolam reduced phosphorylation of ERK1/2 in a time-dependent manner. Washing out propofol after 5 min increased ERK1/2 phosphorylation. The anesthetic-induced depression of ERK1/2 phosphorylation was blocked by 0.1 μM phorbol-12-myristate 13-acetate (an activator of PKC), 50 μM U73122 (an inhibitor of PLC). The anesthetic-induced depression of ERK1 phosphorylation was blocked by 1 mMN-methyl-d-aspartate (NMDA). Whereas 100 μM chelerythrine (an inhibitor of PKC) and 100 μM carbachol (an activator of PLC) and 20 μM PD-98059 (an inhibitor of MEK) had additive effects on propofol-induced inhibition of ERK1/2 phosphorylation. In contrast, 10 μM MK801 (a NMDA receptor antagonist) did not block anesthetic-induced inhibition of ERK1/2 phosphorylation.
  
  
  
  Intravenous anesthetics markedly decreased phosphorylation of ERK1/2 in mouse hippocampal slices, most likely via the NMDA receptor, and PLC- and PKC-dependent pathways. Thus, ERK1/2 represents a target for anesthetics in the brain.
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Xiamen University, Xiamen, PR China.
authors.forename: Gao
authors.initials: G
authors.lastname: Haiying
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Xiamen University, Xiamen, PR China.
authors.forename: Han
authors.initials: H
authors.lastname: Mingjie
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Xiamen University, Xiamen, PR China.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Lingyu
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Xiamen University, Xiamen, PR China.
authors.forename: Wang
authors.initials: W
authors.lastname: Qingxiang
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Xiamen University, Xiamen, PR China.
authors.forename: Wang
authors.initials: W
authors.lastname: Haisong
authors.affiliation: Department of Anesthesiology, Affiliated Beijing Tongren Hospital, Capital University of Medical Science, Beijing, PR China. Electronic address: zbxtryy@126.com.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Bingxi
mesh_terms: D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008807:Mice, Inbred BALB C; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010703:Phorbol Esters / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000187:drug effects* / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D010738:Type C Phospholipases / Q000378:metabolism*
chemical_list: D000777:Anesthetics; D010703:Phorbol Esters; D016194:Receptors, N-Methyl-D-Aspartate; C119222:phorbol-12-myristate; D011493:Protein Kinase C; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D010738:Type C Phospholipases
keywords: Anesthetics; Extracellular signal-regulated Kinase1/2; Hippocampus,Phospholipase C; Phosphorylation; Protein kinase C