Pharmacological characterization of a cloned rat glutamate transporter (GluT-1)

Abstract

Pharmacological properties of a cDNA clone encoding a high affinity, Na +-dependent l-glutamate transporter (GluT-1) were examined using Xenopus oocytes. l-[ 3H]glutamate transport was inhibited by the putative endogenous substrates l-aspartate ( K i = 65 μM) and l-glutamate ( K i = 70 μM). l-Homocysteate did not significantly inhibit high-affinity glutamate transport ( K i = 2.7 mM). Of the previously identified uptake inhibitors, DL-threo-β-hydroxyaspartate ( K i = 65 μM), l-cysteine sulfinate ( K i = 80 μM), β-glutamate ( K i = 475 μM) and l-aspartate-β-hydroxamate ( K i = 950 μM) inhibited l-glutamate uptake. The other l-glutamate uptake blockers examined, including dihydrokainate, l-α-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.