ROLE OF NITRIC OXIDE IN NMDA-EVOKED RELEASE OF [3H]-DOPAMINE FROM STRIATAL SLICES

Abstract

Evidence that excitatory amino acids act via N-methyl-D-aspartate (NMDA) receptors to evoke the release of catecholamines from axonal terminals and synaptosomes has been used to argue for the presence of pre-synaptic NMDA receptors. NMDA receptor agonists also generate nitric oxide (NO) which rapidly diffuses through neural tissue. We find that exogenously applied NO evokes [3H]-dopamine release from cultured neurons. This release is not blocked by the NMDA antagonist MK-801 nor by tetrodotoxin. Both NG-nitroarginine which inhibits NO synthesis, and hemoglobin which binds extracellular NO, block NMDA-evoked [3H]-dopamine release from striatal slices. A major role of endogenously-synthesized NO may be to evoke neurotransmitter release in local volumes of neural tissue.