Group I metabotropic glutamate receptor activation increases phosphorylation of cAMP response element-binding protein, Elk-1, and extracellular signal-regulated kinases in rat dorsal striatum.
Cyclic AMP response element-binding protein (CREB) is a major transcriptional activator at the calcium and cAMP response-element (CaCRE). Phosphorylated (p)CREB facilitates gene expression in striatal neurons. Elk-1 is another transcriptional regulator at the serum response element in the upstream promoter region of the CaCRE. Elk-1 is phosphorylated by extracellular signal-regulated kinases (ERK) and may also contribute to the regulation of gene expression. To evaluate putative roles of group I metabotropic glutamate receptors (mGluRs) in CREB, Elk-1, and ERK phosphorylation, the group I selective agonist, 3,5-dihydroxyphenylglycine (DHPG), was infused into the dorsal striatum at doses of 125, 250, or 500 nmol in freely moving rats. Semi-quantitative immunohistochemistry demonstrated that DHPG significantly increased levels of pCREB, pElk-1, and pERK immunoreactivity of ipsilateral dorsal striatum in a dose dependent manner. The increased immunoreactivity by 500 nmol DHPG was significantly blocked by intrastriatal infusion of the group I selective antagonist, n-phenyl-7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxamide (PHCCC, 25 nmol), but not by the group II/III antagonist, (RS)-alpha-methylserine-o-phosphate monophenyl ester (MSOPPE, 25 nmol). These data suggest that group I mGluR activation is positively linked to signaling cascades resulting in CREB, Elk-1, and ERK phosphorylation in the striatum in vivo.
Choe
E S
ES
Division of Pharmacology, School of Pharmacy, University of Missouri-Kansas City, 2411 Holmes Street, M3-C15, Kansas City, MO, USA.
Wang
J Q
JQ
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001578:Benzopyrans / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D004268:DNA-Binding Proteins; D004305:Dose-Response Relationship, Drug; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives* / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation; D010768:Phosphoserine / Q000031:analogs & derivatives / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014157:Transcription Factors; D050807:ets-Domain Protein Elk-1
D001578:Benzopyrans; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; C494114:Elk1 protein, rat; C442478:N-phenyl-7-(hydroxyimino)cyclopropa(b)chromen-1a-carboxamide; D011518:Proto-Oncogene Proteins; D018094:Receptors, Metabotropic Glutamate; D014157:Transcription Factors; C442477:alpha-methylserine-O-phosphate monophenyl ester; D050807:ets-Domain Protein Elk-1; C104077:metabotropic glutamate receptor type 1; D010768:Phosphoserine; D008734:Methoxyhydroxyphenylglycol; D020928:Mitogen-Activated Protein Kinases; C010117:3,4-dihydroxyphenylglycol