Effect of aluminum on acetyl-CoA and acetylcholine metabolism in nerve terminals.
The potential ability of Al to affect cholinergic transmission was studied on synaptosomal fractions of rat brain incubated with pyruvate in depolarizing medium containing 30 mM K+. Addition of 1 mM Ca caused a 266% increase in the acetylcholine (ACh) release despite decreased pyruvate oxidation. Under these conditions, 0.25 mM Al did not affect pyruvate oxidation but raised mitochondrial and decreased synaptoplasmic acetyl-CoA. Simultaneously, a 61% inhibition of Ca-evoked ACh release was observed. Verapamil (0.1 and 0.5 mM) decreased the acetyl-CoA concentration in synaptoplasm and inhibited ACh release. Al (0.012 mM) partially reversed these inhibitory effects. Omission of Pi from the medium abolished suppressive effects of Al on acetyl-CoA content and Ca-evoked transmitter release. We conclude that the Al(PO4)OH- complex may be the active form of Al, which, by interaction with the verapamil binding sites of Ca channels, is likely to restrict the Ca influx to the synaptoplasm. This may inhibit the provision of acetyl-CoA to the synaptoplasm as well as the Ca-evoked ACh release. One may suppose that excessive accumulation of Al in some encephalopathic brains may, by this mechanism, suppress still-surviving cholinergic neurons and exacerbate cognitive deficits caused by already-existing structural losses in the cholinergic system.
Bielarczyk
H
H
Department of Clinical Biochemistry, Medical University of Gdańsk, Poland.
Tomaszewicz
M
M
Szutowicz
A
A
D000105:Acetyl Coenzyme A / Q000378:metabolism*; D000109:Acetylcholine / Q000096:biosynthesis / Q000378:metabolism*; D000535:Aluminum / Q000494:pharmacology*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002451:Cell Compartmentation / Q000187:drug effects; D019343:Citric Acid / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009411:Nerve Endings / Q000187:drug effects* / Q000378:metabolism*; D010710:Phosphates / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D019289:Pyruvic Acid / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D010710:Phosphates; D019343:Citric Acid; D000105:Acetyl Coenzyme A; D019289:Pyruvic Acid; D014700:Verapamil; D000535:Aluminum; D000109:Acetylcholine; D011188:Potassium