Arachidonic acid depresses non-NMDA receptor currents.

Arachidonic acid has been proposed as an intercellular messenger in the nervous system. It is released when glutamate acts on postsynaptic receptors, potentiates NMDA receptor currents and depresses glutamate uptake. Here we report the effects of arachidonic acid on non-NMDA receptor currents, studied by whole-cell clamping isolated neurons and neurons in tissue slices. In cultured cerebellar granule cells and in freshly isolated hippocampal pyramidal cells arachidonic acid decreased the current produced by iontophoresed AMPA. This depression was not due to increased desensitization of the AMPA receptor. In cerebellar slices, arachidonic acid depressed the non-NMDA component of the synaptic current at the mossy fibre to granule cell and the parallel fibre to Purkinje cell synapses. However, this depression was not always seen, possibly because the lipophilic arachidonic acid is absorbed by superficial cells in the slice and does not reach the synapse being studied. Depression of non-NMDA receptor currents by arachidonic acid may reflect the presence of an arachidonic acid binding site on the non-NMDA receptor, but non-NMDA receptor subunits show much less sequence homology with fatty acid binding proteins than does the NMDA receptor.