Homomeric GluR1 excitatory amino acid receptors expressed in Xenopus oocytes

Abstract

The GluR1 cDNA clone encodes a functional excitatory amino acid receptor (Hollmann et al., Nature 342: 643-648 (1989]. We have studied the pharmacological properties of this homomeric (single subunit) receptor expressed in Xenopus oocytes and compared these properties with those of receptors encoded by rat forebrain mRNA. (RS)-alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionate, quisqualate, and glutamate were partial agonists at both GluR1 and forebrain non-N-methyl-D-aspartate (-NMDA) receptors. The potency of the agonists kainate, domoate, and glutamate was higher, and that of the antagonists 6-cyano-7-nitro-quinoxalinedione and 6,7-dichloro-3-hydroxy-2-quinoxaline carboxylic acid lower, for GluR1 receptors as compared with forebrain non-NMDA receptors. The GluR1 receptor differed strikingly from forebrain-derived non-NMDA receptors, however, in that it exhibited slow, calcium-dependent desensitization. Thus, most properties of the GluR1 receptor are similar but not identical to those of non-NMDA receptors expressed from forebrain mRNA. These results indicate that the ligand recognition sites on GluR1 homomeric receptors are subtly different from those of non-NMDA receptors expressed from a mixture of forebrain mRNA.