PMID- 10095077
OWN - NLM
STAT- MEDLINE
DCOM- 19990513
LR  - 20220309
IS  - 0169-328X (Print)
IS  - 0169-328X (Linking)
VI  - 66
IP  - 1-2
DP  - 1999 Mar 20
TI  - Molecular pathways mediating activation by kainate of mitogen-activated protein 
      kinase in oligodendrocyte progenitors.
PG  - 50-61
AB  - Oligodendroglial cells express ionotropic glutamate receptors of 
      alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid hydrobromide (AMPA) and 
      kainate (KA) subtypes. Recently, we reported that AMPA receptor agonists 
      increased 45Ca2+ uptake and phospholipase C (PLC) activity. To further elucidate 
      the intracellular signaling mechanisms, we examined the effects of AMPA and KA on 
      mitogen-activated protein kinase (MAPK). KA caused a time- and 
      concentration-dependent increase in MAPK activity (predominantly the p42mapk or 
      ERK2) and the effect was blocked by 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX), 
      a competitive AMPA/KA receptor antagonist. Furthermore, the noncompetitive 
      antagonists of AMPA receptor GYKI 52466 and LY 303070 prevented the actions of 
      the agonists, indicating that the effect of KA on MAPK activation is mediated 
      through AMPA receptors in oligodendrocyte progenitors. Chelation of extracellular 
      Ca2+ by EDTA or inhibition of PLC with U73122 abolished MAPK activation by KA. In 
      addition, KA-stimulated MAPK activation was reduced by the protein kinase C (PKC) 
      inhibitors, H7 and bisindolylmaleimide, as well as downregulation of PKC by 
      prolonged exposure to phorbol esters. The involvement of PKC in the signal 
      transduction pathways was further supported by the ability of KA to induce 
      translocation of PKC measured by [3H]PDBu binding. Interestingly, a 
      wortmannin-sensitive phosphatidylinositol 3-kinase and a pertussis toxin 
      (PTX)-sensitive G protein form part of the molecular pathways mediating MAPK 
      activation by AMPA receptor. A specific inhibitor of MAPK kinase, PD 098059, 
      blocked MAPK activation and reduced KA-induced c-fos gene expression. All 
      together, these results indicate that MAPK is implicated in the transmission of 
      AMPA signaling to the nucleus and requires extracellular Ca2+, and PLC/PKC 
      activation.
CI  - Copyright 1999 Elsevier Science B.V.
FAU - Liu, H N
AU  - Liu HN
AD  - Department of Pharmacology and Therapeutics, McGill University, Room 1321, 3655 
      Drummond St., Montreal, Quebec, Canada.
FAU - Larocca, J N
AU  - Larocca JN
FAU - Almazan, G
AU  - Almazan G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Brain Res Mol Brain Res
JT  - Brain research. Molecular brain research
JID - 8908640
RN  - 0 (Androstadienes)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Excitatory Amino Acid Agonists)
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (Flavonoids)
RN  - 0 (Indoles)
RN  - 0 (Maleimides)
RN  - 0 (Proto-Oncogene Proteins c-fos)
RN  - 0 (Receptors, AMPA)
RN  - 0 (Virulence Factors, Bordetella)
RN  - 10028-17-8 (Tritium)
RN  - 6OTE87SCCW (6-Cyano-7-nitroquinoxaline-2,3-dione)
RN  - 77521-29-0 (alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid)
RN  - EC 2.4.2.31 (Pertussis Toxin)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 3.1.4.- (Type C Phospholipases)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
RN  - L79H6N0V6C (bisindolylmaleimide I)
RN  - SIV03811UC (Kainic Acid)
RN  - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)
RN  - SY7Q814VUP (Calcium)
RN  - XVA4O219QW (Wortmannin)
SB  - IM
MH  - 6-Cyano-7-nitroquinoxaline-2,3-dione/pharmacology
MH  - Androstadienes/pharmacology
MH  - Animals
MH  - Animals, Newborn
MH  - Calcium/metabolism
MH  - Calcium-Calmodulin-Dependent Protein Kinases/*metabolism
MH  - Cells, Cultured
MH  - Dose-Response Relationship, Drug
MH  - Enzyme Activation/drug effects
MH  - Enzyme Inhibitors/pharmacology
MH  - Excitatory Amino Acid Agonists/*pharmacology
MH  - Excitatory Amino Acid Antagonists/pharmacology
MH  - Flavonoids/pharmacology
MH  - GTP-Binding Proteins/metabolism
MH  - Indoles/pharmacology
MH  - Kainic Acid/*pharmacology
MH  - Maleimides/pharmacology
MH  - Mitogen-Activated Protein Kinase 1
MH  - Mitogen-Activated Protein Kinase 3
MH  - *Mitogen-Activated Protein Kinases
MH  - Oligodendroglia/chemistry/cytology/*enzymology
MH  - Pertussis Toxin
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Protein Kinase C/metabolism
MH  - Proto-Oncogene Proteins c-fos/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, AMPA/metabolism
MH  - Signal Transduction/physiology
MH  - Stem Cells/chemistry/cytology/*enzymology
MH  - Tritium
MH  - Type C Phospholipases/metabolism
MH  - Virulence Factors, Bordetella/pharmacology
MH  - Wortmannin
MH  - alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/pharmacology
EDAT- 1999/03/30 00:00
MHDA- 1999/03/30 00:01
CRDT- 1999/03/30 00:00
PHST- 1999/03/30 00:00 [pubmed]
PHST- 1999/03/30 00:01 [medline]
PHST- 1999/03/30 00:00 [entrez]
AID - S0169-328X(99)00009-1 [pii]
AID - 10.1016/s0169-328x(99)00009-1 [doi]
PST - ppublish
SO  - Brain Res Mol Brain Res. 1999 Mar 20;66(1-2):50-61. doi: 
      10.1016/s0169-328x(99)00009-1.