Abstract

Effects of diazoxon on the gene and protein expression of nicotinic acetylcholine receptors (nAChR) were evaluated in PC12 cells. Cells were exposed to 100 mu M 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 alpha(4) and beta(2) subunits of nAChR were significantly reduced in cells exposed to diazoxon, but there was no change in alpha(7) subunit mRNA content. Diazoxon exposure also significantly reduced the protein levels of both alpha(4) and beta(2) nAChR subunits. Treatment with nicotine (10 mu M) or with the nicotinic receptor antagonists, mecamylamine (10 mu M) or dihydro-beta-erythroidine (DH beta E) (5 mu M) efficiently prevented the diazoxon-induced reduction in alpha(4) and beta(2) nAChR mRNA and protein in PC12 cells, but carbamaylcholine, a weak nAChR agonist, was ineffective. These data suggest that alpha(4)beta(2) nAChRs are involved in diazoxon-related toxicity and that nicotinic receptor antagonists could play a protective role against organophosphate-related damage. (C) 2008 Elsevier Ltd. All rights reserved.