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C. Schmidt, M. Werner, and M. Hollmann (2006).
Revisiting the postulated “unitary glutamate receptor”: Electrophysiological and pharmacological analysis in two heterologous expression systems fails to detect any evidence for its existence.
Molecular Pharmacology 69(1): 119-129.
doi: 10.1124/mol.105.016840

Several years ago evidence for a so-called “unitary glutamate receptor” was published. This unique type of glutamate receptor was reported to be activated by the classical agonists of all three major glutamate receptor subfamilies, i.e. α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA), kainate (KA), and N-methyl-D-aspartate (NMDA) in a glycine-dependent as well as magnesium-blockable manner and was reported to consist of an NR1 subunit coexpressed with the kainate binding protein (KBP) from Xenopus laevis, XenU1. To re-examine the existence of such a receptor, we cloned two splice variants of the Xenopus NMDA receptor subunit NR1, XenNR1-4a and XenNR1-4b, and expressed them in Xenopus oocytes as well as in HEK293 cells, either alone or with the Xenopus KBP subunit XenU1. In addition, we coexpressed XenU1 separately with all eight splice variants of the rat NR1 subunit. In no case did we see any evidence of a “unitary glutamate receptor” pharmacology. In HEK293 cells we did not get any receptor response unless an NR2 subunit was coexpressed. In Xenopus oocytes, we did observe responses to glutamate/glycine as well as small responses to glycine alone, but these were independent of coexpressed XenU1. Neither AMPA nor kainate ever elicited any significant responses. As we verified that XenU1 is expressed and inserted into the plasma membrane of HEK293 cells, we conclude that XenU1 and NR1 do not form the postulated “unitary glutamate receptor”. Furthermore, successful amplification of a fragment of a Xenopus NR2 subunit indicates that Xenopus utilizes NR2 subunits and not XenU1 to form heteromeric complexes with NR1.