Presynaptic facilitation of glutamate release from isolated hippocampal mossy fiber nerve endings by arachidonic acid.
Hippocampal mossy fiber synaptosomes were used to investigate the role of arachidonic acid in the release of endogenous glutamate and the long-lasting facilitation of glutamate release associated with long-term potentiation. Exogenous arachidonate induced a dose-dependent efflux of glutamate from the hippocampal mossy fiber synaptosomes and this effect was mimicked by melittin. Neither treatment induced the release of occluded lactate dehydrogenase at the concentrations used in these experiments. In each case, removal of the biochemical stimulus allowed for glutamate efflux to return to spontaneous levels. However, there was a persistent effect of exposure to either arachidonate or melittin, since these compounds facilitated the glutamate release induced by the subsequent addition of 35 mM KCl. This facilitation of glutamate release resulted from an enhancement of both the magnitude and duration of the response to depolarization. Although exogenous prostanoids were also able to stimulate the release of glutamate, they appeared to play no direct role in secretion processes, since inhibition of eicosanoid synthesis potentiated the glutamate efflux in response to membrane depolarization or exogenous arachidonic acid. We suggest that the calcium-dependent accumulation of arachidonic acid in presynaptic membranes plays a central role in the release of endogenous glutamate and that the persistent effects of arachidonic acid may be related to the maintenance of long-term potentiation in the hippocampal mossy fiber-CA3 synapse.
Freeman
E J
EJ
Department of Biological Sciences, Kent State University, OH 44242.
Terrian
D M
DM
Dorman
R V
RV
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D005227:Fatty Acids / Q000494:pharmacology; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008555:Melitten / Q000494:pharmacology; D009411:Nerve Endings / Q000187:drug effects / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism; D011189:Potassium Chloride / Q000494:pharmacology; D011453:Prostaglandins / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013574:Synaptosomes / Q000378:metabolism*
D001095:Arachidonic Acids; D005227:Fatty Acids; D005971:Glutamates; D006893:Hydroxyeicosatetraenoic Acids; D011453:Prostaglandins; D008555:Melitten; D016718:Arachidonic Acid; D018698:Glutamic Acid; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D011189:Potassium Chloride; D015761:4-Aminopyridine; D007770:L-Lactate Dehydrogenase; D010741:Phospholipases A