Changes in mRNA and protein levels of nicotinic acetylcholine receptors in Diazoxon exposed pC12 cells.

Effects of diazoxon on the gene and protein expression of nicotinic acetylcholine receptors (nAChR) were evaluated in PC12 cells. Cells were exposed to 100 microM diazoxon for 48 h in the presence versus absence of nAChR agonists or antagonists. Diazoxon significantly inhibited AChE activity in the cells. At the mRNA level, transcripts of the alpha4 and beta2 subunits of nAChR were significantly reduced in cells exposed to diazoxon, but there was no change in alpha7 subunit mRNA content. Diazoxon exposure also significantly reduced the protein levels of both alpha4 and beta2 nAChR subunits. Treatment with nicotine (10 microM) or with the nicotinic receptor antagonists, mecamylamine (10 microM) or dihydro-beta-erythroidine (DHbetaE) (5 microM) efficiently prevented the diazoxon-induced reduction in alpha4 and beta2 nAChR mRNA and protein in PC12 cells, but carbamaylcholine, a weak nAChR agonist, was ineffective. These data suggest that alpha4beta2 nAChRs are involved in diazoxon-related toxicity and that nicotinic receptor antagonists could play a protective role against organophosphate-related damage.