Platelet-activating factor is a messenger in the electroconvulsive shock-induced transcriptional activation of c-fos and zif-268 in hippocampus.
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.
Marcheselli
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VL
Louisiana State University Medical Center, New Orleans 70112.
Bazan
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NG
D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D051766:Early Growth Response Protein 1; D004597:Electroshock / Q000009:adverse effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000378:metabolism*; D017874:Immediate-Early Proteins; D008297:Male; D008861:Microsomes / Q000378:metabolism; D008969:Molecular Sequence Data; D009473:Neuronal Plasticity; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D010980:Platelet Membrane Glycoproteins / Q000187:drug effects; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D012640:Seizures / Q000209:etiology / Q000378:metabolism*; D013570:Synaptic Membranes / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology*; D058924:Thienopyridines; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects; D014230:Triazoles; D016335:Zinc Fingers
D001381:Azepines; D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D017874:Immediate-Early Proteins; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D016760:Proto-Oncogene Proteins c-fos; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D013777:Tetrazoles; D058924:Thienopyridines; D014157:Transcription Factors; D014230:Triazoles; C039351:platelet activating factor receptor; C066686:BN 50730