A new structural class of subtype-selective inhibitor of cloned excitatory amino acid transporter, EAAT2
Research output: Contribution to journal › Journal article › Research › peer-review
We have studied the pharmacological effects of (RS)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA) and the enantiomers of (RS)-2-amino-3-(3-hydroxy-1,2, 5-thiadiazol-4-yl)propionic acid (TDPA) on cloned human excitatory amino acid transporter subtypes 1, 2 and 3 (EAAT1-3) expressed in Cos-7 cells. Whereas AMPA and (R)-TDPA were both inactive as inhibitors of [3H]-(R)-aspartic acid uptake on all three EAAT subtypes, (S)-TDPA was shown to selectively inhibit uptake by EAAT2 with a potency equal to that of the endogenous ligand (S)-glutamic acid. (S)-TDPA thus represents a new structural class of EAAT2 inhibitor that will serve as a lead for the design of EAAT selective inhibitors.
|Journal||European Journal of Pharmacology|
|Publication status||Published - 6 Oct 2000|
- ATP-Binding Cassette Transporters, Amino Acid Transport System X-AG, Animals, Aspartic Acid, Biological Transport, COS Cells, Carrier Proteins, DNA, Recombinant, Excitatory Amino Acid Transporter 2, Glutamate Plasma Membrane Transport Proteins, Receptors, Neurotransmitter, Stereoisomerism, Structure-Activity Relationship, Symporters, Tritium, alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid