Activator protein-1 responsive to the group II metabotropic glutamate receptor subtype in association with intracellular calcium in cultured rat cortical neurons.
Activation of ionotropic glutamate (Glu) receptors, such as N-methyl-d-aspartate receptors, is shown to modulate the gene transcription mediated by the transcription factor activator protein-1 (AP1) composed of Fos and Jun family proteins in the brain, while little attention has been paid to the modulation of AP1 expression by metabotropic Glu receptors (mGluRs). In cultured rat cortical neurons, where constitutive expression was seen with all groups I, II and III mGluR subtypes, a significant and selective increase was seen in the DNA binding activity of AP1 120 min after the brief exposure to the group II mGluR agonist (2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG-IV) for 5 min. In cultured rat cortical astrocytes, by contrast, a significant increase was induced by a group I mGluR agonist, but not by either a group II or III mGluR agonist. The increase by DCG-IV was significantly prevented by a group II mGluR antagonist as well as by either an intracellular Ca(2+) chelator or a voltage-sensitive Ca(2+) channel blocker, but not by an intracellular Ca(2+) store inhibitor. Moreover, DCG-IV significantly prevented the increase of cAMP formation by forskolin in cultured neurons. Western blot analysis revealed differential expression profiles of Fos family members in neurons briefly exposed to DCG-IV and NMDA. Prior or simultaneous exposure to DCG-IV led to significant protection against neuronal cell death by NMDA. These results suggest that activation of the group II mGluR subtype would modulate the gene expression mediated by AP1 through increased intracellular Ca(2+) levels in cultured rat cortical neurons.
Sugiyama
Chie
C
Laboratory of Molecular Pharmacology, Division of Pharmaceutical Sciences, Kanazawa University Graduate School of Natural Science and Technology, Kakuma-machi, Kanazawa, Ishikawa 920-1192, Japan.
Nakamichi
Noritaka
N
Ogura
Masato
M
Honda
Eriko
E
Maeda
Sayaka
S
Taniura
Hideo
H
Yoneda
Yukio
Y
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020013:Calcium Signaling / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism*; D005576:Colforsin / Q000037:antagonists & inhibitors; D000242:Cyclic AMP / Q000378:metabolism; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D007424:Intracellular Fluid / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D002121:Calcium Channel Blockers; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D016760:Proto-Oncogene Proteins c-fos; D018094:Receptors, Metabotropic Glutamate; D018808:Transcription Factor AP-1; C108822:metabotropic glutamate receptor 2; D005576:Colforsin; D000242:Cyclic AMP; D002118:Calcium