Block of the N-methyl-d-aspartate receptor by phenycyclidine-like drugs is influenced by alternative splicing

JoséM M. Rodríguez-Paz, Vellareddy Anantharam, Steven N. Treistman

Research output: Contribution to journalArticle

Abstract

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 (NR1111) subunit, made homomeric assemblies of the receptor more sensitive to ketamine and MK-801 than receptors assembled from NMDAR1 subunits lacking this insert (NR1011 and NR1001). 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 (NR1001) was accompanied by a faster on-rate for drug action than was observed for receptors lacking the insert (NR1011 and NR1001). 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.

Original languageEnglish (US)
Pages (from-to)147-150
Number of pages4
JournalNeuroscience Letters
Volume190
Issue number3
DOIs
StatePublished - May 12 1995

Keywords

  • Anesthesia
  • Ketamine
  • MK-801
  • N-Methyl-d-aspartate

ASJC Scopus subject areas

  • Neuroscience(all)

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