Modulation by L- and D-isoforms of amino acids of the L-glutamate response of N-methyl-D-aspartate receptors.
N-Methyl-D-aspartate (NMDA) receptor subtypes epsilon 1 and zeta 1 were coexpressed in Xenopus oocytes for the investigation of the magnitude of augmentation of the L-glutamate response by 20 common L-amino acids and their 19 D-isoforms. Simultaneous application of L- and D-alanine, -cysteine, and -serine, or glycine and L-glutamate potentiated the glutamate-induced current. Other amino acids produced only marginal effects. Analysis of the relationship between the response and amino acid size revealed that the critical threshold size is between those of cysteine and aspartate. No amino acid alone induced a current. The effects of L- and D-alanine, -cysteine, and -serine applied with L-glutamate were concentration-dependent. Molecular modeling of these three amino acids revealed a positive relationship between the charge at an atom of the side chain and the receptor sensitivity, which may explain the efficacies of these amino acids.
Sakata
K
K
Department of Computer and Information Science, Faculty of Engineering, Iwate University, Japan.
Fukushima
T
T
Minje
L
L
Ogurusu
T
T
Taira
H
H
Mishina
M
M
Shingai
R
R
D000409:Alanine / Q000737:chemistry / Q000502:physiology; D000596:Amino Acids / Q000737:chemistry / Q000502:physiology*; D000818:Animals; D003198:Computer Simulation; D005260:Female; D018698:Glutamic Acid / Q000096:biosynthesis / Q000378:metabolism*; D008024:Ligands; D008564:Membrane Potentials; D009865:Oocytes; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000096:biosynthesis / Q000378:metabolism*; D012694:Serine / Q000737:chemistry / Q000502:physiology; D012984:Software; D013237:Stereoisomerism; D014982:Xenopus laevis
D000596:Amino Acids; D008024:Ligands; D020033:Protein Isoforms; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D012694:Serine; D000409:Alanine