Abstract
Platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine), undetectable in resting neural tissue, accumulates in brain during seizures. A hetrazepine, BN-50730, is shown here to displace [3H]PAF-specific binding from microsomal, but not from synaptosomal membranes, indicating selectivity for a high affinity intracellular binding site. Rats pretreated with BN-50730 by intraperitoneal or intracerebroventricular injection exhibited an inhibition of the electroconvulsive shock (ECS)-induced expression of c-fos and zif-268 in hippocampus. A much more pronounced, dose-dependent inhibition of ECS-induced zif-268 mRNA in hippocampus by intracerebroventricular injection of BN-50730 was observed. It is concluded that, in the hippocampus, PAF is a mediator of the expression of zif-268 and, to a lesser extent, c-fos through an intracellular specific binding site. Thus, PAF may be a messenger in signal regulated zinc-finger transcription factors, and in other immediate-early genes involved in long-term synaptic plasticity changes.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Azepines / pharmacology*
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Base Sequence
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DNA-Binding Proteins / biosynthesis*
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DNA-Binding Proteins / genetics
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Early Growth Response Protein 1
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Electroshock / adverse effects*
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Gene Expression Regulation* / drug effects
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Hippocampus / metabolism*
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Immediate-Early Proteins*
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Male
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Microsomes / metabolism
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Molecular Sequence Data
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Neuronal Plasticity
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Platelet Activating Factor / antagonists & inhibitors
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Platelet Activating Factor / physiology*
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Platelet Membrane Glycoproteins / drug effects
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Proto-Oncogene Proteins c-fos / biosynthesis*
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Proto-Oncogene Proteins c-fos / genetics
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Rats
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Rats, Wistar
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Receptors, Cell Surface*
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Receptors, G-Protein-Coupled*
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Seizures / etiology
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Seizures / metabolism*
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Synaptic Membranes / metabolism
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Tetrazoles / pharmacology*
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Thienopyridines
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Transcription Factors / biosynthesis*
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Transcription Factors / genetics
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Transcription, Genetic / drug effects
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Triazoles*
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Zinc Fingers
Substances
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Azepines
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DNA-Binding Proteins
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Early Growth Response Protein 1
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Egr1 protein, rat
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Immediate-Early Proteins
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Platelet Activating Factor
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Platelet Membrane Glycoproteins
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Proto-Oncogene Proteins c-fos
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Receptors, Cell Surface
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Receptors, G-Protein-Coupled
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Tetrazoles
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Thienopyridines
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Transcription Factors
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Triazoles
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platelet activating factor receptor
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BN 50730