IRON-MEDIATED OXIDATION OF 3,4-DIHYDROXYPHENYLALANINE TO AN EXCITOTOXIN

2,4,5-Trihydroxyphenylalanine (TOPA) oxidizes in solution to form a qu inone derivative that is a non-NMDA glutamatergic agonist and neurotox in. DOPA can autoxidize in physiological solutions to form small amoun ts of both TOPA and TOPA quinone. We report here that this conversion can be dramatically enhanced by iron (II) alone, but more so by iron ( II) in the presence of hydrogen peroxide. This conversion is of suffic ient magnitude that the resulting product can elicit non-NMDA, glutama te receptor-mediated electrical responses in cultured cortical neurons isolated from rat. This finding suggests that TOPA quinone may play a role in pathological processes involving abnormal iron metabolism in catecholaminergic neurons.