δ-Aminolevulinic Acid-Induced Synaptosomal Ca2+Uptake and Mitochondrial Permeabilization

δ-Aminolevulinic acid (ALA) overload is thought to be responsible for the neuropsychiatric manifestations of various porphyric disorders. In fact, ALA-generated oxyradicals have been shown to cause oxidative lesions in rat brain synaptic membranes and to decrease GABAergic receptor affinity. We now describe a stimulatory effect of ALA (1 mM) on Ca2+uptake by cortical synaptosomes and an inhibitory effect on both transmembrane potential and oxygen consumption of intrasynaptosomal mitochondria. Both effects were partly abolished by the addition of antioxidants and the mitochondrial transmembrane potential dissipation observed to be protected by 1 μMruthenium red. Based on these data and on the synaptosomal14C-ALA uptake capacity, we suggest that ALA causes oxidative damage to the mitochondrial membrane. These ALA properties might be involved in the neuropsychiatric porphyric manifestations since enhanced cellular Ca2+uptake and cerebral mitochondria dysfunction seem to be associated with several neurodegenerative processes.