Abstract
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.
| Original language | English |
|---|---|
| Journal | European Journal of Pharmacology |
| Volume | 406 |
| Issue number | 1 |
| Pages (from-to) | 41-4 |
| ISSN | 0014-2999 |
| Publication status | Published - 6 Oct 2000 |
Keywords
- 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