EFFECTS OF PEROXIDATION AND AGING ON RAT NEOCORTICAL ACH-RELEASE AND PROTEIN-KINASE-C

Cerebral cortical synaptosomes were prepared from 2- or 24-month-old F ischer 344 rats and exposed to a peroxidizing condition (50 mu M ferro us ions and 2 mu M ascorbate ions) before measuring either the release of newly synthesized [H-3]acetylcholine (ACh) or protein kinase C act ivity (PKC). Several secretagogues with different mechanisms of action and different responses to aging were used to trigger release: K+ dep olarization (5 mM-60 mM), calcium ionophore A23187 (1-10 mu g/ml), and 4-aminopyridine (0.1-10 mM). Aging reduced K+ depolarization-induced release at every K+ concentration studied, reduced A23187-induced rele ase at low but not high concentrations and did not affect 4-aminopyrid ine-induced release. Membrane peroxidation of synaptosomes from 2-mont h-old rats altered the response to secretagogues to match that seen in 24-month-old rats. Membrane peroxidation also attenuated the A23187-s timulated translocation of free to bound synaptosomal PKC activity in 2-month-old but not 24-month-old animals. These results suggest that m embrane peroxidation may mimic some age-related deficits in secretagog ue-induced [H-3]ACh release.