Putative significance of shifts in acetyl-CoA compartmentalization in nerve terminals for disturbances of cholinergic transmission in brain.
Acetylcholine and acetyl-CoA metabolism in nerve terminals isolated from rat brain were found to be affected by several neurotoxic and neuroprotective agents, such as aluminium, nitric oxide, beta-hydroxybutyrate, verapamil and thiamine deficiency. The changes evoked by these factors in Ca2+-dependent acetylcholine release were highly significantly correlated (r = 0.98) with changes in concentration of synaptoplasmic acetyl-CoA. On the other hand, in the same experimental conditions, no correlation was found between rates of pyruvate oxidation, intramitochondrial acetyl-CoA levels and different pools of releasable acetylcholine. These data indicate that disturbances in the availability of acetyl-CoA in the cytoplasm of nerve terminals may be a key factor in the pathogenesis of several cholinergic encephalopathies.
Department of Clinical Biochemistry, Medical University of Gdańsk, Gdańsk, Poland. aszut@amedec.amg.gda.pl
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Szutowicz
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Tomaszewicz
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Bielarczyk
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Jankowska
D020155:3-Hydroxybutyric Acid / Q000494:pharmacology; D000105:Acetyl Coenzyme A / Q000378:metabolism*; D000535:Aluminum / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000503:physiopathology*; D002799:Cholinergic Fibers / Q000502:physiology*; D008297:Male; D009411:Nerve Endings / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000502:physiology*; D013832:Thiamine Deficiency / Q000378:metabolism; D014018:Tissue Distribution
D020030:Nitric Oxide Donors; D000105:Acetyl Coenzyme A; D000535:Aluminum; D020155:3-Hydroxybutyric Acid