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-[3H]glutamate transport was inhibited by the putative endogenous substrates L-aspartate (Ki = 65 microM) and L-glutamate (Ki = 70 microM). L-Homocysteate did not significantly inhibit high-affinity glutamate transport (Ki = 2.7 mM). Of the previously identified uptake inhibitors, DL-threo-beta-hydroxyaspartate (Ki = 65 microM), L-cysteine sulfinate (Ki = 80 microM), beta-glutamate (Ki = 475 microM) and L-aspartate-beta-hydroxamate (Ki = 950 microM) 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 Ki 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.
Tanaka
K
K
Laboratory for Neural Networks, Institute of Physical and Chemical Research (RIKEN), Saitama, Japan.
D027322:Amino Acid Transport System X-AG; D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D001224:Aspartic Acid / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D003001:Cloning, Molecular; D005260:Female; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D006023:Glycoproteins / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D009865:Oocytes / Q000187:drug effects / Q000502:physiology; D051381:Rats; D014981:Xenopus
D027322:Amino Acid Transport System X-AG; D000596:Amino Acids; D005971:Glutamates; D006023:Glycoproteins; D001224:Aspartic Acid; D018698:Glutamic Acid