NITRIC-OXIDE INHIBITS [H-3] DOPAMINE UPTAKE

Sodium nitroprusside (SNP), a generator of nitric oxide (NO), decrease d [H-3]dopamine uptake into rat striatal synaptosomal preparations in a dose-, time- and temperature-dependent fashion. Reduced hemoglobin, a substance that binds NO, prevented the SNP-induced decrease in uptak e. Potassium ferri- and ferrocyanide, compounds similar to SNP that do not produce NO, were without effect on uptake. SNP inhibited [H-3]dop amine uptake in synaptosomes from nucleus accumbens and olfactory tube rcle as well but with a lower potency. SNP inhibited [H-3]serotonin an d [H-3]glutamate uptake but had no effect on [H-3]norepinephrine uptak e. S-Nitroso-N-acetylpenicillamine (SNAP), another generator of NO, ha d effects similar to those of SNP. The SNP-induced decrease in [H-3]do pamine uptake was due to a V(max) decrease at 100 muM SNP and to both a V(max) and K(m) change at 300 muM SNP. Depletion of calcium by omiss ion of calcium from buffers and addition of EGTA increased the potency of SNP in inhibiting uptake. There was no change in [H-3]WIN 35428 bi nding to the dopamine transporter with doses of SNP that inhibited upt ake. These data indicate that NO can decrease [H-3]dopamine transporte r function.