Effects of delta-aminolaevulinic acid, porphobilinogen and structurally related amino acids on 2-deoxy-glucose uptake in cultured neurons

Abstract

The effects of delta-aminolaevulinic acid (ALA), porphobilinogen (PBG), gamma amino-butyric acid (GABA), muscimol, glutamic acid and kainic acid on [3H]2-deoxy-D-glucose uptake by cultured neurons were investigated. Exposure to the cultures for 4 days, to ALA at concentrations as low as 10 microM 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 minimum 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.