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

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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 (Ki = 65 μM) and l-glutamate (Ki = 70 μM). l-Homocysteate did not significantly inhibit high-affinity glutamate transport (Ki = 2.7 mM). Of the previously identified uptake inhibitors, DL-threo-β-hydroxyaspartate (Ki = 65 μM), l-cysteine sulfinate (Ki = 80 μM), β-glutamate (Ki = 475 μM) and l-aspartate-β-hydroxamate (Ki = 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 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.

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    I thank Dr. M. Ito for continuous encouragement. This work was supported by Special Researchers' Basic Science Program from the Institute of Physical and Chemical Research (RIKEN).

    Present address: Department of Degenerative Neurological Diseases, National Institute of Neuroscience, NCNP, 4-1-1 Ogawahigashi-cho, Kodaira, Tokyo 187, Japan. Fax: (81) (423) 46-1745.

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