Yang_1991_Fundam.Appl.Toxicol_17_34

This swine trachea study was undertaken to examine the effects of nerve agents on mucus gland cell function. Subacute treatment of swine with soman, sarin, and VX inhibits acetylcholinesterase and leads to down-regulation of muscarinic receptors in tracheal submucosal gland cells. Muscarinic receptor density in isolated cells as determined by [3H]QNB binding was reduced by 60-65% and that measured using [3H]NMS was decreased by 65-73%. Subacute treatment of swine for 7 days with soman and VX caused a small, significant increase in the fraction of receptors with high affinity for carbachol. The decrease in receptor density was accompanied by a decrease in acetylcholine-induced mucus secretion. The decrease in mucus secretion was not due to a decrease in the ability of the cells to produce or release mucus since cross-tolerance did not develop to methoxamine-induced mucus secretion. Therefore, we conclude that in mucus gland cells tolerance development can be linked functionally to muscarinic receptor loss.