Enhancement of hippocampal excitatory synaptic transmission by platelet-activating factor.
The biologically active lipid platelet-activating factor (1-O-alkyl-2-acetyl-sn-glycero-3-phosphorylcholine; PAF) is a mediator of inflammatory and immune responses, and it accumulates in the brain during convulsions or ischemia. We have examined whether PAF may play a second messenger role in the central nervous system by studying effects on synaptic transmission in cultured hippocampal neurons. Carbamyl-PAF, a nonhydrolyzable PAF analog with a similar pharmacologic profile, augmented glutamate-mediated, evoked excitatory synaptic transmission and increased the frequency of spontaneous miniature excitatory synaptic events without increasing their amplitude or altering their time course. This compound had no significant effect on gamma-aminobutyric acid-mediated inhibitory synaptic responses. Lyso-PAF, the biologically inactive metabolic intermediate, had no effect on synaptic transmission. Moreover, the enhancement of excitatory synaptic transmission by carbamyl-PAF was blocked by a PAF receptor antagonist. These results indicate a specific presynaptic effect of PAF in enhancing excitatory synaptic transmission in cultured rat hippocampal neurons.
Clark
G D
GD
Department of Neurology, Louisiana State University Medical School, New Orleans 70112-2234.
Happel
L T
LT
Zorumski
C F
CF
Bazan
N G
NG
D000818:Animals; D000831:Animals, Newborn; D001640:Bicuculline / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D009924:Organ Culture Techniques; D010972:Platelet Activating Factor / Q000494:pharmacology*; D051381:Rats; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects*; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D010972:Platelet Activating Factor; D005680:gamma-Aminobutyric Acid; D001640:Bicuculline