Effects of fructose-1,6-bisphosphate on glutamate release and ATP loss from rat brain slices during hypoxia.
Fructose-1,6-bisphosphate (FBP), an intermediate of glucose metabolism, is neuroprotective in brain hypoxia or ischemia. Because the mechanisms for this protection are not clear, we examined the effects of FBP on two important events in brain ischemia, i.e., loss of ATP and release of the excitatory neurotransmitter glutamate. Glutamate release from cortical brain slices was measured fluorometrically (glutamate dehydrogenase-catalyzed conversion of glutamate to alpha-ketoglutarate) during hypoxia (PO2 15 mm Hg) or hypoxia plus 100 microM cyanide. FBP (3.5 mM, with glucose 20 mM) reduced glutamate release during hypoxia by 55% and during hypoxia/cyanide by 46% (p < 0.005), and prevented a significant fall in [ATP]. [ATP] was maintained in oxygenated glucose-free conditions with 20 but not 3.5 mM FBP, and fell to < 20% of normal with hypoxia. Despite the drop in [ATP], 3.5 or 20 mM FBP without glucose decreased hypoxia-evoked glutamate release. We conclude (1) FBP present without glucose preserves normal [ATP] only when oxygen is available, suggesting limited uptake and metabolism; and (2) FBP decreases hypoxia-evoked glutamate release by processes independent of [ATP]. These results suggest protective actions of FBP that are separate from augmentation of anaerobic energy production, as previously proposed.
Bickler
P E
PE
Department of Anesthesia, University of California, San Francisco, USA.
Buck
L T
LT
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015687:Cell Hypoxia; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D003486:Cyanides / Q000494:pharmacology; D005635:Fructosediphosphates / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D010455:Peptides / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D003486:Cyanides; D005635:Fructosediphosphates; D010455:Peptides; D018698:Glutamic Acid; D011189:Potassium Chloride; D000255:Adenosine Triphosphate; D020866:omega-Conotoxin GVIA; C029063:fructose-1,6-diphosphate