title: Glutamate receptor agonists increase the expression of Fos, Fra, and AP-1 DNA binding activity in the mammalian brain.
abstract: Administration of convulsant doses of Metrazole (pentylenetetrazol) and picrotoxin, as well as maximal electroshock, results in a rapid but transient increase in c-fos mRNA in mouse brain. Elevation of c-fos mRNA is followed by the accumulation and subsequent disappearance of Fos, the protein encoded by c-fos. In addition, immunoblots reveal the induction of two additional proteins that are antigenically related to Fos (Fra, Fos-related antigens). Fos and the various Fra appear and disappear in a staggered manner over an 8 hour period, such that at longer times after stimulation the brain contains no Fos but relatively large amounts of Fra (the latter being designated here by their apparent molecular weights, Fra-46K and Fra-35K). Previous studies have established that Fos, as well as several Fra, contribute to transcription factor AP-1 nucleoprotein complexes along with Jun, the product of the jun proto-oncogene. The appearance in brain of Fos and Fra coincides with a protracted increase in total AP-1 DNA binding activity, indicating that all the Fos-like proteins can participate in AP-1 complexes. Furthermore, the molecular composition of these complexes alters with time after stimulation. The induction of c-fos by Metrazole is blocked or attenuated by known anticonvulsants such as diazepam and valproate as well as the N-methyl-D-aspartate (NMDA) receptor antagonists, 2-amino-5-phosphonovaleric acid (APV) and MK-801. This suggests that fos induction might involve stimulation of a glutamate receptor. This conclusion was strengthened by the observations that two glutamate receptor agonists, kainic acid and NMDA, induced c-fos expression.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Neuroscience, Roche Institute of Molecular Biology, Roche Research Center, Nutley, New Jersey 07110.
authors.forename: J L
authors.initials: JL
authors.lastname: Sonnenberg
authors.forename: C
authors.initials: C
authors.lastname: Mitchelmore
authors.forename: P F
authors.initials: PF
authors.lastname: Macgregor-Leon
authors.forename: J
authors.initials: J
authors.lastname: Hempstead
authors.forename: J I
authors.initials: JI
authors.lastname: Morgan
authors.forename: T
authors.initials: T
authors.lastname: Curran
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001224:Aspartic Acid / Q000494:pharmacology; D001667:Binding, Competitive; D015152:Blotting, Northern; D003292:Convulsants / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D004597:Electroshock; D005786:Gene Expression Regulation / Q000187:drug effects*; D015151:Immunoblotting; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016202:N-Methylaspartate; D009693:Nucleic Acid Hybridization; D010433:Pentylenetetrazole / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger / Q000096:biosynthesis; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis
chemical_list: D000927:Anticonvulsants; D001224:Aspartic Acid; D003292:Convulsants; D004268:DNA-Binding Proteins; D007608:Kainic Acid; D016202:N-Methylaspartate; D010433:Pentylenetetrazole; D010852:Picrotoxin; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter; D014157:Transcription Factors