Abstract
In vivo activation of group I metabotropic glutamate receptors (mGluRs) upregulates phosphorylation of cyclic AMP response element-binding protein (CREB), Elk-1 and extracellular signal-regulated kinases (ERK) in striatal neurons. To evaluate putative roles of Ca2+/calmodulin-dependent protein kinase II (CaMKII) in CREB, Elk-1 and ERK phosphorylation, the CaMKII inhibitor, KN62, was infused simultaneously with the group I mGluR agonist, 3,5-dihydroxyphenylglycine (DHPG), into the rat dorsal striatum. The results showed that DHPG (125, 250, and 500 nmol) increased phosphorylated (p) CaMKII immunoreactivity (IR) in a dose-dependent manner. KN62 (50 nmol) significantly attenuated 500 nmol DHPG-induced pERK, pElk-1 and pCREB IR in the ipsilateral dorsal striatum. These data indicate that pCaMKII is a possible upstream effector that is responsible for the regulation of CREB, Elk-1 and ERK phosphoproteins in response to group I mGluR stimulation in striatal neurons.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Calcium-Calmodulin-Dependent Protein Kinase Type 2
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Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
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Corpus Striatum / drug effects
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Corpus Striatum / metabolism*
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Cyclic AMP Response Element-Binding Protein / metabolism*
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DNA-Binding Proteins*
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Enzyme Inhibitors / pharmacology
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Excitatory Amino Acid Agonists / pharmacology
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Glycine / analogs & derivatives
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Glycine / pharmacology
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Immunohistochemistry
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Male
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Microinjections
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Mitogen-Activated Protein Kinases / metabolism*
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Phosphorylation / drug effects
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Proto-Oncogene Proteins / metabolism*
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Rats
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Rats, Wistar
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Receptors, Metabotropic Glutamate / agonists
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Receptors, Metabotropic Glutamate / metabolism*
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Resorcinols / pharmacology
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Signal Transduction / physiology
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Transcription Factors*
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ets-Domain Protein Elk-1
Substances
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Cyclic AMP Response Element-Binding Protein
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DNA-Binding Proteins
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Elk1 protein, rat
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Enzyme Inhibitors
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Excitatory Amino Acid Agonists
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Proto-Oncogene Proteins
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Receptors, Metabotropic Glutamate
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Resorcinols
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Transcription Factors
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ets-Domain Protein Elk-1
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3,5-dihydroxyphenylglycine
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Calcium-Calmodulin-Dependent Protein Kinase Type 2
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Calcium-Calmodulin-Dependent Protein Kinases
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Mitogen-Activated Protein Kinases
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Glycine