L-GLUTAMATE-EVOKED RELEASE OF DOPAMINE FROM SYNAPTOSOMES OF THE RAT STRIATUM - INVOLVEMENT OF AMPA AND N-METHYL-D-ASPARTATE RECEPTORS

Previously, using purified synaptosomes from the rat striatum, we have shown that agonists of D,L-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors stimulate the release of [H-3]dopamine continuously synthesized from [H-3]tyrosine, Similar results were obtained with N-methyl-D-aspartate in the absence of magnesium. In the present study, using the same approach, attempts were made to determine whether in the presence of magnesium, the combined stimulation of AMPA receptors allows us to demonstrate the presynaptic facilitation of [H-3]dopamine release through N-methyl-D-aspartate receptors. L-Glutamate (10(-3) M) markedly stimulated the release of [H-3]dopamine from synaptosomes, this effect being about twice that found with AMPA (10(-3) M) while N-methyl-D-aspartate (10(-3) M) even in the presence of glycine (10(-6) M) was ineffective. In agreement with previous results, a stimulatory effect of N-methyl-D-aspartate and glycine was only observed in the absence of magnesium. This response was blocked by 6,7-dinitro-quinoxaline-2,3-dione (3 x 10(-5) M), confirming that this compound, generally used as an AMPA antagonist, also blocks N-methyl-D-aspartate receptors. The AMPA (10(-3) M)-evoked release of [H-3]dopamine was markedly potentiated by the combined application of N-methyl-D-aspartate (10(-3) M) and glycine (10(-6) M) in the presence of strychnine, indicating that the concomitant activation of AMPA receptors removes the voltage-dependent magnesium block of N-methyl-D-aspartate receptors. The L-glutamate (10(-3) M)-evoked release of [H-3]dopamine was potentiated by glycine (10(-6) M). only partially reduced by (+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclohepten-5,1-imine maleate (MK801) (10(-5) M) and almost completely abolished by 6,7-dinitro-quinoxaline-2,3-dione (3 x 10(-5) M). In addition. the L-glutamate (10(-3) M)-evoked release of [H-3]dopamine was of similar amplitude in either the presence or absence of magnesium. Altogether. these results demonstrate that L-glutamate, in high concentration. facilitates the release of [H-3]dopamine from rat striatal synaptosomes by acting both on AMPA and N-methyl-D-aspartate receptors, even in the presence of magnesium.