PT  - JOURNAL ARTICLE
AU  - Wahl, Philip
AU  - Anker, Charlotte
AU  - Traynelis, Stephen F.
AU  - Egebjerg, Jan
AU  - Rasmussen, Jesper S.
AU  - Krogsgaard-Larsen, Povl
AU  - Madsen, Ulf
TI  - Antagonist Properties of a Phosphono Isoxazole Amino Acid at Glutamate R1–4 (<em>R,S</em>)-2-Amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic Acid Receptor Subtypes
AID  - 10.1124/mol.53.3.590
DP  - 1998 Mar 01
TA  - Molecular Pharmacology
PG  - 590--596
VI  - 53
IP  - 3
4099  - http://molpharm.aspetjournals.org/content/53/3/590.short
4100  - http://molpharm.aspetjournals.org/content/53/3/590.full
SO  - Mol Pharmacol1998 Mar 01; 53
AB  - The activity of the (R,S)-2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid (AMPA) receptor antagonist, (R,S)-2-amino-3-[5-tert-butyl-3-(phosphonomethoxy)-4-isoxazolyl]propionic acid (ATPO), at recombinant ionotropic glutamate receptors (GluRs) was evaluated using electrophysiological techniques. Responses at homo- or heterooligomeric AMPA-preferring GluRs expressed in human embryonic kidney (HEK) 293 cells (GluR1-flip) or Xenopus laevisoocytes (GluR1–4-flop or GluR1-flop + GluR2) were potently inhibited by ATPO with apparent dissociation constants (K b values) ranging from 3.9 to 26 μm. A Schild analysis for kainate (KA)-activated GluR1 receptors showed ATPO to have aK B of 8.2 μmand a slope of unity, indicating competitive inhibition. The antagonism by ATPO at GluR1 was of similar magnitude at holding potentials between −100 mV and +20 mV. In contrast, ATPO (<300 μm), does not inhibit responses to kainate at homomeric GluR6 or heterooligomeric GluR6/KA2 expressed in HEK 293 cells but activated GluR5 and GluR5/KA2 expressed in X. laevis oocytes. ATPO produced <15% inhibition at the maximal concentration (300 μm) of current responses through NR1A + NR2B receptors expressed in X. laevis oocytes. Thus, ATPO shows a unique pharmacological profile, being an antagonist at GluR1–4 and a weak partial agonist at GluR5 and GluR5/KA2.