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

JoséM 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
Externally publishedYes

Fingerprint

Alternative Splicing
Phencyclidine
Dizocilpine Maleate
Ketamine
Xenopus
Aspartic Acid
Pharmaceutical Preparations
Oocytes
Protein Isoforms
Amino Acids
Messenger RNA
NMDA receptor A1
aspartic acid receptor
midkine receptors

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Block of the N-methyl-d-aspartate receptor by phenycyclidine-like drugs is influenced by alternative splicing. / Rodríguez-Paz, JoséM; Anantharam, Vellareddy; Treistman, Steven N.

In: Neuroscience Letters, Vol. 190, No. 3, 12.05.1995, p. 147-150.

Research output: Contribution to journalArticle

Rodríguez-Paz, JoséM ; Anantharam, Vellareddy ; Treistman, Steven N. / Block of the N-methyl-d-aspartate receptor by phenycyclidine-like drugs is influenced by alternative splicing. In: Neuroscience Letters. 1995 ; Vol. 190, No. 3. pp. 147-150.
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