Neurosci Lett 1995 May 12;1903:147-50. doi: 10.1016/0304-3940(95)11524-z.

Block of the N-methyl-D-aspartate receptor by phencyclidine-like drugs is influenced by alternative splicing.

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N-Methyl-D-aspartate (NMDA) receptors were expressed in Xenopus oocytes from injected mRNA. The presence of an alternatively-spliced insertion encoding 21 amino acids at the N-terminus of the NMDAR1 (NR1(111)) subunit, made homomeric assemblies of the receptor more sensitive to ketamine and MK-801 than receptors assembled from NMDAR1 subunits lacking this insert (NR1(011) and NR1(001)). The influence of this insert was maintained when NR1 subunits were co-expressed in heteromeric combinations with NR2B. The increased sensitivity of the receptors containing the insert (NR1(111)) was accompanied by a faster on-rate for drug action than was observed for receptors lacking the insert (NR1(011) and NR1(001)). Our results suggest that the action of phencyclidine-like drugs is influenced by the presence of Insertion I in the NMDA isoforms, generated by alternative splicing.

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Species referenced: Xenopus
Genes referenced: grin1 grin2b