Activation of p44/p42 MAP kinase in striatal neurons via kainate receptors and PI3 kinase.
The members of the mitogen-activated protein (MAP) kinase family -- p44/p42 MAP kinase (ERK), c-jun N-terminal kinase (JNK) and p38 MAP kinase (p38) are known to be important mediators of the physiological plasticity or neurotoxicity induced in the striatum by activation of ionotropic glutamate receptors. However, our knowledge of the class of glutamate receptor and the intracellular pathways involved derives totally from studies on embryonic neurons, where the mechanisms are likely to be totally different from those operating in mature neurons. In superfused striatal slices from adult rats, NMDA and kainate, but not AMPA, were found to activate ERK. No activation of p38 or JNK was detected following treatment with any ionotropic glutamate receptor agonist. The activation of ERK by kainate was blocked by the ERK kinase (MEK) inhibitor PD98059, and the PI3 kinase inhibitor wortmannin, but not by the p38 MAP kinase inhibitor SB203580. This provides evidence for a novel pathway linking striatal kainate receptors to ERK activation via PI3 kinase and MEK.
Fuller
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G
Division of Neuroscience and Biomedical Systems, Institute of Biomedical and Life Sciences, West Medical Building, University of Glasgow, Glasgow G12 8QQ, UK.
Veitch
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K
Ho
L K
LK
Cruise
L
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Morris
B J
BJ
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D003342:Corpus Striatum / Q000166:cytology*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases; D007608:Kainic Acid / Q000494:pharmacology; D048670:MAP Kinase Kinase 4; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000201:enzymology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism; D018092:Kainic Acid Receptors / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D000077191:Wortmannin; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000730:Androstadienes; D016291:Dizocilpine Maleate; D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D005419:Flavonoids; D007093:Imidazoles; D048031:JNK Mitogen-Activated Protein Kinases; D007608:Kainic Acid; D048670:MAP Kinase Kinase 4; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020929:Mitogen-Activated Protein Kinase Kinases; D020928:Mitogen-Activated Protein Kinases; D016202:N-Methylaspartate; D019869:Phosphatidylinositol 3-Kinases; D011725:Pyridines; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D000077191:Wortmannin; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one