Stimulation of synaptosomal D-[(3)H]aspartate transport by substance P in rat brain

The effect of the neuropeptide, substance P, on the transport of D-[(3)H]aspartate into rat striatal synaptosomes was studied. Almost 90% of the total transport of D-[(3)H]aspartate was sodium-dependent and the maximum rate (V(max)) of this transport was increased by 34% of control by 2.5 nM substance P (EC(50)=0.52 nM). In contrast, sodium-independent transport was inhibited by substance P. The NK(1) antagonist, L706303 (500 nM) blocked the stimulation of D-[(3)H]aspartate transport by 2.5 nM substance P, but did not alter D-aspartate uptake in the absence of substance P. These results indicate that high affinity glutamate transporters in the brain may be under positive regulation by substance P, and suggest a previously-unidentified mechanism of control of glutamate transport.