Pharmacological properties of homomeric and heteromeric GluR1o and GluR3o receptors
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Homomeric and heteromeric alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor subunits GluR1o and GluR3o were expressed in Spodoptera frugiperda (Sf9) insect cells. Membranes containing the recombinant receptors showed a doublet of bands of the expected size (99-109 kDa) after western immunoblotting which was shifted to a single band upon deglycosylation. In (R,S)-[3H]AMPA binding experiments, high expression was seen (Bmax = 0.8-3.8 pmol/mg protein) along with high affinity binding to a single site (Kd, nM+/-S.D.): GluR1o, 32.5+/-2.7; GluR3o, 23.7+/-2.4; GluR1o + GluR3o, 18.1+/-2.9. The pharmacological profiles of these receptors resembled that of native 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 (R,S)-2-amino-3-(3-carboxy-5-methyl-4-isoxazolyl)propionate (ACPA) exhibited an 11-fold selectivity for GluR3o vs. GluR1o. In this study, it was found that ACPA has 3-fold higher affinity at homomeric GluR3o and heteromeric receptors than at homomeric GluR1o, suggesting that its efficacy and/or desensitisation properties are different at GluR1o vs. GluR3o.
Original language | English |
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Journal | European Journal of Pharmacology |
Volume | 360 |
Issue number | 2-3 |
Pages (from-to) | 227-38 |
Number of pages | 11 |
ISSN | 0014-2999 |
Publication status | Published - 1998 |
Bibliographical note
Keywords: Animals; Baculoviridae; Binding, Competitive; Blotting, Western; Glutamic Acid; Glycosylation; Mutagenesis; Radioligand Assay; Receptors, AMPA; Recombinant Proteins; Spodoptera; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
ID: 20122784