Regulation of immediate early gene c-fos and zif/268 mRNA expression in rat striatum by metabotropic glutamate receptor.
Metabotropic glutamate receptors are coupled to multiple intracellular second messenger systems through G-proteins and densely expressed by medium spiny projection neurons in the rat striatum. In chronically-cannulated rats, this study demonstrated that pharmacological activation of metabotropic glutamate receptors by intrastriatal injection of a selective agonist, ACPD, elevated immediate early gene c-fos and zif/268 mRNA expression in the injected dorsal striatum as revealed by quantitative in situ hybridization. The elevation of both c-fos and zif/268 was dose-dependent and the responsiveness of c-fos to ACPD at each dose surveyed was greater than that of zif/268. Induction of the two mRNAs was rapid and transient as increases in the 2 mRNAs became evident as early as 30 min, reached a peak at 1 h, and returned to normal levels 3 (c-fos) or 6 (zif/268) h, after ACPD injection. Coadministration of the selective metabotropic glutamate receptor antagonist, MCPG, with ACPD markedly attenuated ACPD-stimulated c-fos, but not zif/268, expression. Pretreatment with the ionotropic NMDA receptor antagonist, CPP, had no effect on ACPD-stimulated c-fos expression, but partially attenuated ACPD-stimulated zif/268 expression. Blockade of D1 dopamine receptors with SCH-23390 did not alter the ability of ACPD to induce the expression of these genes. These data demonstrate a difference between the profound induction of c-fos and zif/268 gene expression in response to specific activation of metabotropic glutamate receptors in striatal neurons. Furthermore, c-fos induction was independent of D1 dopaminergic and NMDA glutamatergic transmission, whereas zif/268 induction was mediated, at least in part, by NMDA receptors.
Wang
J Q
JQ
Department of Pharmacology, Howard University College of Medicine, 520 W Street NW, Washington, DC 20059, USA. jwang@hucmphrm.howard.edu
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D001565:Benzoates / Q000494:pharmacology; D003342:Corpus Striatum / Q000737:chemistry* / Q000502:physiology; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D051766:Early Growth Response Protein 1; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D017781:Genes, Immediate-Early / Q000502:physiology*; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D017874:Immediate-Early Proteins; D017403:In Situ Hybridization; D008297:Male; D008845:Microinjections; D018696:Neuroprotective Agents / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics*; D016335:Zinc Fingers / Q000235:genetics
D001552:Benzazepines; D001565:Benzoates; D004268:DNA-Binding Proteins; D018492:Dopamine Antagonists; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D018691:Excitatory Amino Acid Antagonists; D017874:Immediate-Early Proteins; D018696:Neuroprotective Agents; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D017447:Receptors, Dopamine D1; D018094:Receptors, Metabotropic Glutamate; D014157:Transcription Factors; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; C079694:alpha-methyl-4-carboxyphenylglycine; D005998:Glycine