DELTA-AMINOLEVULINIC ACID-INDUCED SYNAPTOSOMAL CA2+ UPTAKE AND MITOCHONDRIAL PERMEABILIZATION

delta-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 oxidativ e lesions in rat brain synaptic membranes and to decrease GABAergic re ceptor 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 m itochondria. Both effects were partly abolished by the addition of ant ioxidants and the mitochondrial transmembrane potential dissipation ob served to be protected by 1 mu M ruthenium red. Based on these data an d on the synaptosomal C-14-ALA uptake capacity, we suggest that ALA ca uses oxidative damage to the mitochondrial membrane. These ALA propert ies might be involved in the neuropsychiatric porphyric manifestations since enhanced cellular Ca2+ uptake and cerebral mitochondria dysfunc tion seem to be associated with several neurodegenerative processes. ( C) 1996 Academic Press, Inc.