Substrate specificity of the mammary tissue anionic amino acid carrier operating in the cotransport and exchange modes

The substrate specificity of the rat mammary tissue high affinity, Naf-dependent anionic amino acid transport system has been investigated using explants and the perfused mammary gland. D-Aspartate appears to be transported via the high affinity, Na+-dependent L-glutamate carrier. Thus, D-aspartate transport by rat mammary tissue was Nas-dependent and saturable with respect to extracellular D-aspartate with a K-m and V-max of 32.4 mu M and 49.0 nmol/2 min per g of cells respectively. The uptake of D-aspartate by mammary explants was cis-inhibited by L-glutamate and L-aspartate, but not by D-glutamate. L-glutamate uptake by mammary tissue explants was cis-inhibited by P-glutamate, L-cysteate, L-cysteine sulfinate and dihydrokainate but not by DL-alpha-aminoadipate. In addition, dihydrokainate, but not DL-alpha-aminoadipate inhibited D-aspartate and L-glutamate uptake by the perfused gland. D-Aspartate efflux from mammary tissue explants was a-ans-accelerated by external L-glutamate in a dose-dependent fashion (50-500 mu M). The effect of L-glutamate on D-aspartate efflux was dependent on the presence of extracellular Na+. D-Aspartate, L-aspartate and L-cysteine sulfinate (at 500 mu M) also markedly trans-stimulated D-aspartate efflux from mammary tissue explants, In contrast, L-cysteine, D-glutamate, L-leucine, dihydrokainate and DL-alpha-aminoadipate were either weak stimulators of D-aspartate efflux or were without effect. D-Aspartate efflux from the perfused mammary gland was trans-stimulated by L-glutamate but not by D-glutamate and only weakly by L-cysteine (all at 500 mu M). It appears that the mammary tissue high affinity anionic amino acid carrier can operate in the exchange mode with a similar substrate specificity to that of the co-transport mode.