Effects of membrane peroxidation on [3H]acetylcholine release in rat cerebral cortical synaptosomes

[3H]Acetylcholine (ACh) release, malonaldehyde formation and 45calcium-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 [3H]ACh. Combined exposure to Fe2+/ascorbate also reduced calcium ionophore A23187-induced [3H]ACh release. Neither ferrous nor ascorbate ions alone altered depolarization- or ionophore-induced [3H]ACh release over this concentration range. Depolarization- and A23187-induced 45calcium 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.