[Mechanism of delta-aminolevulinic acid neurotoxicity].
The neurotoxicity of delta-aminolaevulinic acid (ALA), porphobilinogen (PBG), glutamic acid, gamma-aminobutyric acid and kainic acid was compared in order to investigate the possibility of a common neurotoxic mechanism. Only ALA (10 microM) 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.
D000622:Aminolevulinic Acid / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D003342:Corpus Striatum / Q000187:drug effects; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D007608:Kainic Acid / Q000494:pharmacology; D007982:Levulinic Acids / Q000494:pharmacology*; D009417:Nerve Tissue / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects*; D011162:Porphobilinogen / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D005971:Glutamates; D007982:Levulinic Acids; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D011162:Porphobilinogen; D000622:Aminolevulinic Acid; D007608:Kainic Acid
'n Ondersoek na die meganisme van delta-aminolevuliniensuur-neurotoksisiteit.