EFFECTS OF MEMBRANE PEROXIDATION ON [H-3] ACETYLCHOLINE-RELEASE IN RAT CEREBRAL CORTICAL SYNAPTOSOMES

[H-3]Acetylcholine (ACh) release, malonaldehyde formation and calcium-45-uptake were measured in rat cerebral cortical nerve terminal that were exposed to various concentrations of ferrous and ascorbate ions. At a constant molar ratio of 25:1, ferrous:ascorbate, these ions increased malonaldehyde (MA) synthesis in a concentration-dependent manner. Treatment with these ions in the same ratio also induced a dose-related inhibition of the K+-depolarization-induced release of newly synthesized [H-3]ACh. Combined exposure to Fe2+/ascorbate also reduced calcium ionophore A23187-induced [H-3]ACh release. Neither ferrous nor ascorbate ions alone altered depolarization- or ionophore-induced [H-3]ACh release over this concentration range. Depolarization- and A23187-induced calcium-45 uptake were not affected by peroxidation, suggesting that membrane peroxidation influenced some process in the release-process subsequent to calcium influx in a manner similar to what is observed during aging.