Arachidonic acid induces a prolonged inhibition of glutamate uptake into glial cells.
Activation of NMDA (N-methyl-D-aspartate) receptors by neurotransmitter glutamate stimulates phospholipase A2 to release arachidonic acid. This second messenger facilitates long-term potentiation of glutamatergic synapses in the hippocampus, possibly by blocking glutamate uptake. We have studied the effect of arachidonic acid on glutamate uptake into glial cells using the whole-cell patch-clamp technique to monitor the uptake electrically. Micromolar levels of arachidonic acid inhibit glutamate uptake, mainly by reducing the maximum uptake rate with only small effects on the affinity for external glutamate and sodium. On removal of arachidonic acid a rapid (5 minutes) phase of partial recovery is followed by a maintained suppression of uptake lasting at least 20 minutes. Surprisingly, the action of arachidonic acid is unaffected by cyclo-oxygenase or lipoxygenase inhibitors suggesting that it inhibits uptake directly, possibly by increasing membrane fluidity. As blockade of phospholipase A2 prevents the induction of long-term potentiation (LTP), inhibition of glutamate uptake by arachidonic acid may contribute to the increase of synaptic gain that occurs in LTP. During anoxia, release of arachidonic acid could severely compromise glutamate uptake and thus contribute to neuronal death.
Barbour
B
B
Department of Physiology, University College London, UK.
Szatkowski
M
M
Ingledew
N
N
Attwell
D
D
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D005071:Evoked Potentials / Q000187:drug effects; D005971:Glutamates / Q000378:metabolism*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007700:Kinetics; D009637:Masoprocol / Q000494:pharmacology; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D019301:Oleic Acid; D009829:Oleic Acids / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D012160:Retina; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014562:Caudata
D001095:Arachidonic Acids; D005971:Glutamates; D009829:Oleic Acids; D016718:Arachidonic Acid; D019301:Oleic Acid; C011459:elaidic acid; D010042:Ouabain; D009637:Masoprocol; D013755:Tetradecanoylphorbol Acetate; D007213:Indomethacin