PHARMACOLOGICAL PROPERTIES OF HOMOMERIC AND HETEROMERIC GLUR1(O) AND GLUR3(O) RECEPTORS

Homomeric and heteromeric pha-amino-3-hydroxy-5-methyl-4-isoxazoleprop ionate (AMPA) receptor subunits GluR1(o) and GluR3(o) were expressed i n Spodoptera frugiperda (Sf9) insect cells. Membranes containing the r ecombinant receptors showed a doublet of bands of the expected size (9 9-109 kDa) after western immunoblotting which was shifted to a single band upon deglycosylation. In (R,S)-[H-3]AMPA binding experiments, hig h expression was seen (B-max = 0.8-3.8 pmol/mg protein) along with hig h affinity binding to a single site (K-d, nM +/- S.D.): GluR1(o), 32.5 +/- 2.7; GluR3(o), 23.7 +/- 2.4; GluR1(o) + GluR3(o), 18.1 +/- 2.9. T he pharmacological profiles of these receptors resembled that of nativ e rat brain AMPA receptors: AMPA analogues > L-glutamate > quinoxaline -2,3-diones > kainate. In the Xenopus oocyte expression system we had previously shown that the agonist mino-3-(3-carboxy-5-methyl-4-isoxazo lyl)propionate (ACPA) exhibited an 11-fold selectivity for GluR3(o) vs . GluR1(o). In this study, it was found that ACPA has similar to 3-fol d higher affinity at homomeric GluR3(o) and heteromeric receptors than at homomeric GluR1(o), suggesting that its efficacy and/or desensitis ation properties are different at GluR1(o) vs. GluR3(o). (C) 1998 Else vier Science B.V. All rights reserved.