Influence of ammonia, octanoate, quinolinate and hypoxic conditions on NAD(P)H fluorescence of hippocampal slices.
Acute exposure of rat hippocampal slices to high concentrations of the neurotoxicants, ammonia, octanoate and quinolinate, was monitored by microscope fluorimetry and NAD(P)H absorption. High concentrations of ammonia or octanoate, or a combination of both, reduced the fluorescence signals under aerobic conditions to a similar extent as observed in the case of CN(?)-induced model hypoxia. Quinolinate alone did not produce any effect, nor was it effective in the presence of ammonia or octanoate. Ammonia or octanoate or a combination of both neurotoxicants being present, administration of 2-oxoglutarate or valine was found to prevent efficiently changes in fluorimetric response in a protective manner. The results are interpreted as being supportive of the notion that these compounds may entail a mechanism of protective potency. Glutamate being substituted for glucose of the normal incubation medium, addition of ammonia produced higher oxidation states of nicotinamide nucleotides (K(m app) = 16.9 mM; SD = 3.1; n = 7) only when excessive ammonia concentrations were chosen. Hence, it is conjectured that glutamate uptake and metabolization are not essentially reduced by ammonia levels even in the case of severe hyperammonaemia.
Markefski
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Institute of Biology, Medical Academy of Magdeburg, Erich-Weinert-Strasse 3, D/O-3014 Magdeburg, F.R.G.
Wolf
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