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Effects of δ-aminolaevulinic acid, porphobilinogen and structurally related amino acids on 2-deoxyglucose uptake in cultured neurons

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Abstract

The effects of δ-aminolaevulinic acid (ALA), porphobilinogen (PBG), γ-aminobutyric acid (GABA), muscimol, glutamic acid and kainic acid on [3H]2-deoxy-d-glucose uptake by cultured neurons were investigated. Exposure of the cultures for 4 days, to ALA at concentrations as low as 10 μM caused a significant, dose-dependent decrease in [3H]2-deoxy-d-glucose uptake. Neither ALA nor PBG appeared to interfere directly with glucose transport into the neuron but 1 mM ALA caused an initial stimulation of [3H]2-deoxy-d-glucose uptake which increased to a maximum after 4 hr and fell to below control values after 19 hr exposure. GABA and muscimol caused similar increases in [3H]2-deoxy-d-glucose uptake but these values remained above control levels after 19 hr exposure. Glutamic acid and kainic acid caused an immediate increase in [3H]2-deoxy-d-glucose uptake which declined to mininum values after 4 hr exposure. The effect of ALA on glucose utilization in neurons may be of particular relevance to patients with acute porphyria where a genetic lesion in neural haem and haemoprotein biosynthesis is postulated to occur. ALA appeared to be more toxic to the neurons than any of the other compounds tested, possibly causing a critical depletion of energy reserves and cell death.

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Russell, V.A., Lamm, M.C.L. & Taljaard, J.J.F. Effects of δ-aminolaevulinic acid, porphobilinogen and structurally related amino acids on 2-deoxyglucose uptake in cultured neurons. Neurochem Res 7, 1009–1022 (1982). https://doi.org/10.1007/BF00965140

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