Inhibition of Na+, K+-ATPase activity by δ-aminolevulinic acid
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δ-Aminolaevulinic acid (ALA) has been shown to be toxic to cultured neurons and glia at concentrations as low as 10 μM. In an attempt to elucidate the mechanism of toxicity, the effects of ALA on membrane ATPase activity were investigated. Exposure of neuron cultures to 1 mM ALA for 7 days caused a substantial decrease in both Na+, K+-ATPase and Mg2+-ATPase activities. At lower concentrations, ALA affected only the Na+, K+-component. ALA appeared to act directly, inhibiting Na+, K+-ATPase activity in rat brain cortex membrane preparations at 10 μM Although this effect was slight, it may well represent the mechanism of action of ALA, since ouabain, a potent inhibitor of Na+, K+-ATPase activity, proved to be more toxic to cultured neurons than ALA. Furthermore, cardiac glycoside overdosage causes neurological disturbances which are very similar to those observed in the acute attack of porphyria.
KeywordsGlycoside ATPase Activity Potent Inhibitor Ouabain Acute Attack
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