A comparison of some metabolic effects of N-methylaspartate stereoisomers, glutamate and depolarization: a multinuclear MRS study.
Exposure of guinea pig brain slices to low concentrations (10 microM) of NMDA caused decreases in PCr and ATP within 30 min, with a slower decrease in NAA and increase in lactate, both detectable after 1 h. Exposure to NMDA for over 1 h or at higher concentrations caused further increases in lactate and decreases in NAA, with no further change in PCr or ATP. The L-isomer, NMLA, and the racemic mixture, NMDLA, caused similar changes in lactate and NAA, but both produced greater decreases in the energy state than NMDA, similar to those caused by prolonged exposure to glutamate. MK-801 prevented the changes in the energy state caused by NMDA, but not those caused by NMLA or by glutamate. The results are compared to previous studies on depolarization and discussed in terms of the role of the NMDA sub-type of glutamate receptor in the excitotoxic hypothesis of neuronal degeneration.
Thatcher
N M
NM
M. R. Centre, School of Physics & Astronomy, University of Nottingham, UK.
Badar-Goffer
R S
RS
Ben-Yoseph
O
O
McLean
M A
MA
Morris
P G
PG
Prior
M J W
MJ
Taylor
A
A
Bachelard
H S
HS
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004594:Electrophysiology; D004734:Energy Metabolism / Q000187:drug effects; D018690:Excitatory Amino Acid Agonists / Q000737:chemistry / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D018698:Glutamic Acid / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D019344:Lactic Acid / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D016202:N-Methylaspartate / Q000737:chemistry / Q000494:pharmacology*; D009994:Osmolar Concentration; D010725:Phosphocreatine / Q000378:metabolism; D013237:Stereoisomerism
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D010725:Phosphocreatine; D001224:Aspartic Acid; D019344:Lactic Acid; D018698:Glutamic Acid; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D000255:Adenosine Triphosphate; C000179:N-acetylaspartate; D005947:Glucose