The development of age-related deficits in several presynaptic processes associated with brain [3H]acetylcholine release.
Isolated nerve terminals were prepared from the neocortices and striate cortices of Fischer 344 rats from 6 to 26 months of age and then assayed for release of newly synthesized [3H]acetylcholine (ACh) triggered by secretagogues with different mechanisms of action: 35 mM K+, 10 microM veratridine and 5 microM A23187. Secretagogue-induced release of newly synthesized [3H]ACh decreased with age in both brain regions, with reductions in A23187-induced release paralleling those seen with depolarizing agents. This observation was consistent with the hypothesis that aging attenuates the release-triggering ability of calcium ions coincident with or before it affects voltage-sensitive calcium influx. In neocortex, phorbol-stimulated translocation of protein kinase C (PKC) activity was attenuated in isolated nerve terminals concomitantly with A23187-induced release deficits. These results suggest that one of the earliest deficits in the ACh-release process may involve intracellular calcium potency, which may be associated with the onset of functional PKC deficits. Both brain regions also displayed gradual, age-related reductions in [3H]ACh synthesis, but this effect was more pronounced in the striatum. Choline acetyltransferase (CAT) activity decreased only in the striatum with aging.
Meyer
E M
EM
Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Health Science Center, Gainesville 32610-0267.
Judkins
J H
JH
D000109:Acetylcholine / Q000378:metabolism*; D000375:Aging / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D015500:Chloramphenicol O-Acetyltransferase / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology; D014793:Visual Cortex / Q000187:drug effects / Q000378:metabolism
D000001:Calcimycin; D014701:Veratridine; D015500:Chloramphenicol O-Acetyltransferase; D011493:Protein Kinase C; D000109:Acetylcholine; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium