In vivo glutamine hydrolysis in the formation of extracellular glutamate in the injured rat brain.
Hydrolysis of extracellular glutamine as a potential source of increased extracellular glutamate in the quinolinic acid (QUIN)-injured brain of the unanesthetized, free-moving rat was examined by microdialysis and HPLC analysis. Injury was initiated by injection of 100 nmoles of QUIN into the hippocampus. Immediately postinjury or 24 hr postinjury, the injection site was perfused with artificial cerebrospinal fluid + (14)C-glutamine to measure its conversion to (14)C-glutamate. L-trans-pyrrolidine-2,4-dicarboxylate (L-PDC), a glutamate uptake inhibitor, was added to the perfusate to enhance the detection of extracellular (14)C-glutamate. QUIN injury was followed by an immediate increase in extracellular glutamate that persisted 24 hr later. When (14)C-glutamine was added to the perfusate, a significant amount of (14)C-glutamate was recovered, and it was greater following QUIN injury than in control animals (P < 0.001). Up to 32% of the extracellular (14)C-glutamine was converted to (14)C-glutamate following QUIN injury. Considering the high concentration of glutamine normally present in the extracellular fluid, glutamine hydrolysis is a potential and important source for the increase in extracellular glutamate after neuronal injury in vivo.
Mena
F V
FV
Department of Pediatrics, University of Maryland School of Medicine, Baltimore 21201-1559, USA.
Baab
P J
PJ
Zielke
C L
CL
Zielke
H R
HR
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D001930:Brain Injuries / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism*; D018698:Glutamic Acid / Q000032:analysis / Q000096:biosynthesis*; D005973:Glutamine / Q000378:metabolism*; D006868:Hydrolysis; D008297:Male; D017551:Microdialysis; D009410:Nerve Degeneration / Q000139:chemically induced / Q000503:physiopathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D018690:Excitatory Amino Acid Agonists; D005973:Glutamine; D018698:Glutamic Acid