Arachidonic acid and oleoylacetylglycerol induce a synergistic facilitation of Ca(2+)-dependent glutamate release from hippocampal mossy fiber nerve endings.
Arachidonic acid and oleoylacetylglycerol enhance depolarization-evoked glutamate release from hippocampal mossy fiber nerve endings. It was proposed this is a Ca(2+)-dependent effect and that protein kinase C is involved. Here we report that arachidonic acid and oleoylacetylglycerol synergistically potentiate the glutamate release induced by the Ca2+ ionophore ionomycin. The Ca2+ dependence of this effect was established, as removal of Ca2+ eliminated evoked release and the lipid-dependent potentiation. Also, Ca2+ channel blockers attenuated ionomycin- and KCl-evoked exocytosis, as well as the facilitating effects of the lipid mediators. Although facilitation required Ca2+, it may not involve an enhancement of evoked Ca2+ accumulation, because ionomycin-dependent glutamate release was potentiated under conditions that did not increase ionomycin-induced Ca2+ accumulation. Also, the facilitation may not depend on inhibition of K+ efflux, because enhanced release was observed in the presence of increasing concentrations of 4-aminopyridine and diazoxide did not reduce the lipid-dependent potentiation of exocytosis. In contrast, disruption of cytoskeleton organization with cytochalasin D occluded the lipid-dependent facilitations of both KCl- and ionomycin-evoked glutamate release. In addition, arachidonic acid plus glutamatergic or cholinergic agonists enhanced glutamate release, whereas a role for protein kinase C in the potentiation of exocytosis was substantiated using kinase inhibitors. It appears that the lipid-dependent facilitation of glutamate release from mossy fiber nerve endings requires Ca2+ and involves multiple presynaptic effects, some of which depend on protein kinase C.
Zhang
L
L
Department of Biological Sciences, Kent State University, Ohio 44242, USA.
Ruehr
M L
ML
Dorman
R V
RV
D015761:4-Aminopyridine / Q000494:pharmacology; D000200:Action Potentials; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D018678:Cholinergic Agents / Q000494:pharmacology; D015638:Cytochalasin D / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects / Q000502:physiology; D003981:Diazoxide / Q000494:pharmacology; D004075:Diglycerides / Q000494:pharmacology*; D004357:Drug Synergism; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D005089:Exocytosis / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D009411:Nerve Endings / Q000187:drug effects* / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D013268:Stimulation, Chemical; D009435:Synaptic Transmission / Q000187:drug effects
D002121:Calcium Channel Blockers; D018678:Cholinergic Agents; D004075:Diglycerides; D018683:Excitatory Amino Acid Agents; D007476:Ionophores; D015638:Cytochalasin D; D016718:Arachidonic Acid; D018698:Glutamic Acid; D015759:Ionomycin; C038237:1-oleoyl-2-acetylglycerol; D015761:4-Aminopyridine; D011493:Protein Kinase C; D003981:Diazoxide; D011188:Potassium; D002118:Calcium