Inhibition by folded isomers of L-2-(carboxycyclopropyl)glycine of glutamate uptake via the human glutamate transporter hGluT-1.
The effects of isomers of 2-(carboxycyclopropyl)glycine (CCG) on uptake of L-glutamate were investigated in COS-7 cells that expressed a cloned human glutamate transporter (hGluT-1). The (2S, 3S, 4R)-isomer (L-CCG-III) and the (2S, 3R, 4S)-isomer (L-CCG-IV) markedly inhibited glutamate uptake with a 50% inhibitory concentration of 290 nM and 1.1 microM, respectively. The (2S, 3S, 4S)-isomer (L-CCG-I) and the (2S, 3R, 4R)-isomer (L-CCG-II) did not inhibit glutamate uptake at concentrations of < or = 10 microM. Thus, hGluT-1 showed a markedly higher affinity for L-CCG-III and L-CCG-IV with a folded conformation of the glutamate skeleton, than for L-CCG-I or L-CCG-II with an extended conformation.
Yamashita
H
H
Third Department of Internal Medicine, Hiroshima University School of Medicine, Japan.
Kawakami
H
H
Zhang
Y X
YX
Hagiwara
T
T
Tanaka
K
K
Nakamura
S
S
D018528:ATP-Binding Cassette Transporters / Q000494:pharmacology*; D027322:Amino Acid Transport System X-AG; D000600:Amino Acids, Dicarboxylic / Q000494:pharmacology*; D002478:Cells, Cultured; D018076:DNA, Complementary; D004305:Dose-Response Relationship, Drug; D018698:Glutamic Acid / Q000378:metabolism / Q000494:pharmacology; D005998:Glycine / Q000494:pharmacology*; D006801:Humans; D014162:Transfection
D018528:ATP-Binding Cassette Transporters; D027322:Amino Acid Transport System X-AG; D000600:Amino Acids, Dicarboxylic; D018076:DNA, Complementary; C035261:(alpha-carboxycyclopropyl)glycine; D018698:Glutamic Acid; D005998:Glycine