Evaluation of nicotinic receptors agonists and antagonists against paraoxon exposed PC12 cells

Chronic and acute exposure to organophosphate pesticides may lead to persistent neurological and neurobehavioral effects, which cannot be explained by acetylcholinesterase (AChE) inhibition alone. In an attempt to elucidate the mechanism by which paraoxon affects the nicotinic receptors gene expression, the effects of exposure of PC12 cells to 100 μM concentrations of paraoxon for 48 h in the presence and the absence of nicotinic acetylcholine receptors (nAChRs) agonists and antagonists were characterized. Paraoxon at 100 μM significantly inhibited AChE activity. On the mRNA level, the α4 and β2 subunits of nAChR mRNA were significantly decreased in the cells exposed to paraoxon. On the protein level, α4 and β2 subunits of nAChR protein were also significantly reduced. Mecamylamine (10 μM), dihydro-β-erythroidine (DHβE) (5 μM) and nicotine (10 μM) efficiently prevented the decrease of α4 and β2 nAChR mRNA and protein in PC12 cells, but carbamaylcholine a weak agonist of nAChR was not efficient. These observations suggest that α4β2 nAChRs are involved in paraoxon related toxicity and nicotinic receptors antagonists could play some protective role against organophosphate related damages.