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 Fischer 344 rats and exposed to a peroxidizing condition (50 microM ferrous ions and 2 microM ascorbate ions) before measuring either the release of newly synthesized [3H]acetylcholine (ACh) or protein kinase C activity (PKC). Several secretagogues with different mechanisms of action and different responses to aging were used to trigger release: K+ depolarization (5 mM-60 mM), calcium ionophore A23187 (1-10 micrograms/ml), and 4-aminopyridine (0.1-10 mM). Aging reduced K+ depolarization-induced release at every K+ concentration studied, reduced A23187-induced release at low but not high concentrations and did not affect 4-aminopyridine-induced release. Membrane peroxidation of synaptosomes from 2-month-old rats altered the response to secretagogues to match that seen in 24-month-old rats. Membrane peroxidation also attenuated the A23187-stimulated translocation of free to bound synaptosomal PKC activity in 2-month-old but not 24-month-old animals. These results suggest that membrane peroxidation may mimic some age-related deficits in secretagogue-induced [3H]ACh release.
Meyer
E M
EM
Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville 32610-0267.
Judkins
J H
JH
Momol
A E
AE
Hardwick
E O
EO
D015761:4-Aminopyridine / Q000494:pharmacology; D000109:Acetylcholine / Q000378:metabolism*; D000375:Aging / Q000378:metabolism*; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D002794:Choline / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010545:Peroxides / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D013570:Synaptic Membranes / Q000201:enzymology / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*
D009419:Nerve Tissue Proteins; D010545:Peroxides; D000001:Calcimycin; D015761:4-Aminopyridine; D011493:Protein Kinase C; D002794:Choline; D000109:Acetylcholine; D011188:Potassium