PHARMACOLOGICAL CHARACTERIZATION OF A CLONED RAT GLUTAMATE TRANSPORTER (GLUT-1)

Pharmacological properties of a cDNA clone encoding a high affinity, Na+-dependent L-glutamate transporter (GluT-1) were examined using Xenopus oocytes. L-[H-3]glutamate transport was inhibited by the putative endogenous substrates L-aspartate (K-i = 65 mu M) and L-glutamate (K-i = 70 mu M). L-Homocysteate did not significantly inhibit high-affinity glutamate transport (K-i = 2.7 mM). Of the previously identified uptake inhibitors, DL-threo-beta-hydroxyaspartate (K-i = 65 mu M), L-cysteine sulfinate (K-i = 80 mu M), beta-glutamate (K-i = 475 mu M) and L-aspartate-beta-hydroxamate (K-i = 950 mu M) inhibited L-glutamate uptake. The other L-glutamate uptake blockers examined, including dihydrokainate, L-alpha-aminoadipate and SITS, weakly inhibited uptake of L-glutamate with K-i values in excess of 1 mM. These features of the inhibitor sensitivities of GluT-1 transport show that GluT-1 is less sensitive to these agents than previously characterized glutamate transporters in rat brain, suggesting that GluT-1 is a novel glutamate transporter with a unique pharmacologic profile.