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

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 (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.

journal_name

Neurosci Lett

journal_title

Neuroscience letters

authors

Rodríguez-Paz JM,Anantharam V,Treistman SN

doi

10.1016/0304-3940(95)11524-z

subject

Has Abstract

pub_date

1995-05-12 00:00:00

pages

147-50

issue

3

eissn

0304-3940

issn

1872-7972

pii

030439409511524Z

journal_volume

190

pub_type

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