Establishment of CHO cell lines expressing four N-methyl-D-aspartate receptor subtypes and characterization of a novel antagonist PPDC.
To develop an assay system that allows the N-methyl-D-aspartate (NMDA) receptor subtype-selective antagonistic potency of drugs, we have established Chinese hamster ovary cell lines expressing the four NMDA receptor subtypes (GluRepsilon1/zeta1-GluRepsilon4/zeta1) heat-indelibly. Using these clonal cells, we found that a novel antagonist, (1S,2R)-1-phenyl-2[(S)-1-aminopropyl]-N,N-diethylcyclopropanecarboxamide, was less selective for the GluRepsilon1/zeta1: the IC(50) values for the GluRepsilon1/zeta1-GluRepsilon4/zeta1 were 41.7, 13.3, 12.6 and 11.5 microM, respectively, while two well-known antagonists, DL-2-amino-5-phosphonovaleric acid and ifenprodil, showed the known potency and selectivity for each subtype. Thus, the established clonal cells are of use in characterizing the pharmacological properties of drugs that act on NMDA receptors.
Uchino
S
S
Department of Neurochemistry, National Institute of Neuroscience, Kodaira, Tokyo, Japan. uchino@ncnp.go.jp
Watanabe
W
W
Nakamura
T
T
Shuto
S
S
Kazuta
Y
Y
Matsuda
A
A
Nakajima-Iijima
S
S
Kudo
Y
Y
Kohsaka
S
S
Mishina
M
M
D000818:Animals; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism; D006224:Cricetinae; D003521:Cyclopropanes / Q000494:pharmacology*; D004594:Electrophysiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000502:physiology; D018698:Glutamic Acid / Q000494:pharmacology; D005998:Glycine / Q000494:pharmacology; D006358:Hot Temperature; D010880:Piperidines / Q000494:pharmacology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology
C438901:1-phenyl-2-(1-aminopropyl)-N,N-diethylcyclopropanecarboxamide; D003521:Cyclopropanes; D018691:Excitatory Amino Acid Antagonists; D010880:Piperidines; D020033:Protein Isoforms; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; C056639:2-amino-5-phosphopentanoic acid; D014633:Valine; C010739:ifenprodil; D002118:Calcium; D005998:Glycine