ARACHIDONIC-ACID AND OLEOYLACETYLGLYCEROL INDUCE A SYNERGISTIC FACILITATION OF CA2-DEPENDENT GLUTAMATE RELEASE FROM HIPPOCAMPAL MOSSY FIBERNERVE-ENDINGS()

Arachidonic acid and oleoylacetylglycerol enhance depolarization-evoke d glutamate release from hippocampal messy fiber nerve endings. It was proposed this is a Ca2+-dependent effect and that protein kinase C is involved. Here we report that arachidonic acid and oleoylacetylglycer ol synergistically potentiate the glutamate release induced by the Ca2 + ionophore ionomycin. The Ca2+ dependence of this effect was establis hed, as removal of Ca2+ eliminated evoked release and the lipid-depend ent potentiation. Also, Ca2+ channel blockers attenuated ionomycin- an d KCl-evoked exocytosis, as well as the facilitating effects of the li pid mediators. Although facilitation required Ca2+, it may not involve an enhancement of evoked Ca2+ accumulation, because ionomycin-depende nt glutamate release was potentiated under conditions that did not inc rease ionomycin-induced Ca2+ accumulation. Also, the facilitation may not depend on inhibition of K+ efflux, because enhanced release was ob served in the presence of increasing concentrations of 4-aminopyridine and diazoxide did not reduce the lipid-dependent potentiation of exoc ytosis, In contrast, disruption of cytoskeleton organization with cyto chalasin D occluded the lipid-dependent facilitations of both KCl- and ionomycin-evoked glutamate release. In addition, arachidonic acid plu s glutamatergic or cholinergic agonists enhanced glutamate release, wh ereas a role for protein kinase C in the potentiation of exocytosis wa s substantiated using kinase inhibitors. It appears that the lipid-dep endent facilitation of glutamate release from messy fiber nerve ending s requires Ca2+ and involves multiple presynaptic effects, some of whi ch depend on protein kinase C.