bn-50730 and Seizures

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.

Topics: Animals; Azepines; Base Sequence; DNA-Binding Proteins; Early Growth Response Protein 1; Electroshock; Gene Expression Regulation; Hippocampus; Immediate-Early Proteins; Male; Microsomes; Molecular Sequence Data; Neuronal Plasticity; Platelet Activating Factor; Platelet Membrane Glycoproteins; Proto-Oncogene Proteins c-fos; Rats; Rats, Wistar; Receptors, Cell Surface; Receptors, G-Protein-Coupled; Seizures; Synaptic Membranes; Tetrazoles; Thienopyridines; Transcription Factors; Transcription, Genetic; Triazoles; Zinc Fingers