delta-Aminolaevulinic acid uptake, toxicity, and effect on [14C]gamma-aminobutyric acid uptake into neurons and glia in culture

Abstract

delta-Aminolaevulinic acid (ALA) uptake into neurons and glia in primary culture as well as ALA toxicity and its effects on gamma-aminobutyric acid (GABA) uptake were examined. [4-14C]ALA uptake into neurons and glia was nonsaturable, partially Na+- and temperature-dependent, and appeared to comprise mainly diffusion into the cell. 2,4-Dinitrophenol caused some inhibition of [4-14C]ALA uptake whereas ouabain, KCN, or amino acids at 1 mM concentration were without effect. ALA (1 mM) caused a slight inhibition of [U-14C]GABA uptake into neurons (14%) and glia (9%), but was without effect at lower concentrations. It is unlikely that, in acute porphyria, ALA reaches sufficiently high levels in nervous tissue to interfere with the reuptake of GABA into neurons or glia. ALA was shown to be toxic, judged by the loss of cells, to both neurons and glia at concentrations as low as 10 microM. Such a concentration of ALA may be expected to occur in the CSF of porphyric patients in the acute attack. However, results obtained with dispersed cells in culture may not necessarily reflect the situation in vivo where the cell may have a far greater resistance to the effects of toxic agents.