Premium
Effects of Fructose‐1,6‐Bisphosphate on Glutamate Release and ATP Loss from Rat Brain Slices During Hypoxia
Author(s) -
Bickler Philip E.,
Buck Leslie T.
Publication year - 1996
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1996.67041463.x
Subject(s) - glutamate receptor , hypoxia (environmental) , endocrinology , neuroprotection , medicine , ischemia , neurotransmitter , chemistry , cyanide , biology , biochemistry , oxygen , pharmacology , central nervous system , receptor , inorganic chemistry , organic chemistry
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 α‐ketoglutarate) during hypoxia (Po 2 15 mm Hg) or hypoxia plus 100 µ M cyanide. FBP (3.5 m M , with glucose 20 m M ) 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 m M FBP, and fell to <20% of normal with hypoxia. Despite the drop in [ATP], 3.5 or 20 m M 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.