3-Acetylpyridine (3AP) is a potent neurotoxin when administered to laboratory animals. However, its neurotoxic effects have not been investigated extensively in vitro. Cultured cerebellar granule cells are killed by concentrations of 3AP of 0.1-1 mM (ED50 = 220 μM) but not by its 2-acetyl and 4-acetyl analogues. The toxicity of 3AP is enhanced by preexposure to subtoxic concentrations of N-methyl-d-aspartate (NMDA) and is unaffected by the NMDA receptor antagonists MK-801 or APV, as well as by deprenyl, mazindol, or tetrahydrofolic acid. However, 3AP toxicity is completely blocked by preincubating cerebellar granule cells with low concentrations of niacinamide. These data lead us to suggest that 3AP toxicity is due to the substitution of 3AP for niacinamide in the formation of niacinamide adenine dinucleotides (NAD(P)).
- Cerebellar granule cell