title: Potentiation of nuclear activator protein-1 DNA binding following brief exposure to N-methyl-D-aspartate in immature cultured rat hippocampal neurons.
abstract: Similar potentiation was seen with the nuclear transcription factor activator protein-1 (AP1) binding in rat hippocampal neurons cultured for 3 and 9 DIV, when determined immediately after exposure to 500 microM N-methyl-D-aspartate (NMDA) for 60-120 min. Growth-associated protein-43 was markedly expressed in hippocampal neurons cultured for 3-5 DIV, with a decline up to 9 DIV. In immature neurons cultured for 3 DIV, NMDA was effective in significantly potentiating AP1 binding even in the presence of Mg(2+) with less potency than in the absence of Mg(2+) when determined immediately after sustained exposure for 120 min. When determined 120 min after brief exposure for 5 min, by contrast, NMDA significantly potentiated AP1 binding at a range of 100-500 microM only in the absence of Mg(2+) in immature neurons cultured for 3 DIV. At least 60 min was required for significant potentiation of AP1 binding as an interval between brief exposure and subsequent cell harvest. Dizocilpine abolished the potentiation determined 120 min after brief exposure to 500 microM NMDA, and both dantrolene and nifedipine were similarly effective in significantly preventing the potentiation at 10-50 microM. These results suggest that NMDA may potentiate AP1 binding following a sustained increase in intracellular free Ca(2+) concentrations through influxes across NMDA-operated and L-type voltage-sensitive Ca(2+) channels, in addition to release from intracellular Ca(2+) stores, in immature cultured rat hippocampal neurons.
authors.affiliation: Department of Molecular Pharmacology, Kanazawa University Faculty of Pharmaceutical Sciences, Kanazawa, Ishikawa 920-0934, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Hirai
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Kuramoto
authors.forename: Hiroko
authors.initials: H
authors.lastname: Maruyama
authors.forename: Vladimir J
authors.initials: VJ
authors.lastname: Balcar
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Yukio
authors.initials: Y
authors.lastname: Yoneda
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005333:Fetus; D006624:Hippocampus / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D016202:N-Methylaspartate / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000187:drug effects / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D018808:Transcription Factor AP-1; D016202:N-Methylaspartate; D004247:DNA