An investigation into the mechanism of delta-aminolaevulinic acid neurotoxicity
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The neurotoxicity of δ-aminolaevulinic acid (ALA), porphobilinogen (PBG), glutamic acid, γ-aminobutyric acid and kainic acid was compared in order to investigate the possibility of a common neurotoxic mechanism. Only ALA (10 μM) and glutamic acid (1 mM) were toxic towards neurons in culture, as measured by cell survival after 5 days' exposure. 3H-kainic acid binds to striatal membranes with an equilibrium dissociation constant (KD) of 57 nM and the number of binding sites was found to be 20 pmol/g striatal tissue. However, neither of the porphyrin precursors could displace kainic acid from these binding sites. Kainic acid alone caused neuronal degeneration after intrastriatal administration, as determined by 3H-spiroperidol binding to striatal membranes. The porphyrin precursors ALA and PBG thus do not share a common neurotoxic mechanism with the well-known neurotoxin kainic acid.
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