TY - JOUR
T1 - Block of the N-methyl-d-aspartate receptor by phenycyclidine-like drugs is influenced by alternative splicing
AU - Rodríguez-Paz, JoséM M.
AU - Anantharam, Vellareddy
AU - Treistman, Steven N.
N1 - Funding Information:
This work was supported by NIH grant 5 R03 DA07555. NMDAR2B cDNA was kindly provided by Dr. Dolan Pritchett, University of Pennsylvania Medical School. We thank Andrew Wilson for his technical assistance.
PY - 1995/5/12
Y1 - 1995/5/12
N2 - 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.
AB - 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.
KW - Anesthesia
KW - Ketamine
KW - MK-801
KW - N-Methyl-d-aspartate
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U2 - 10.1016/0304-3940(95)11524-Z
DO - 10.1016/0304-3940(95)11524-Z
M3 - Article
C2 - 7637880
AN - SCOPUS:0029030812
SN - 0304-3940
VL - 190
SP - 147
EP - 150
JO - Neuroscience Letters
JF - Neuroscience Letters
IS - 3
ER -