Yang C M, Dwyer T M, Farley J M
Department of Pharmacology/Toxicology, University of Mississippi Medical Center, Jackson 39216-4505.
Fundam Appl Toxicol. 1991 Jul;17(1):34-42. doi: 10.1016/0272-0590(91)90236-w.
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.
开展这项猪气管研究是为了检测神经毒剂对黏液腺细胞功能的影响。用梭曼、沙林和VX对猪进行亚急性处理会抑制乙酰胆碱酯酶，并导致气管黏膜下腺细胞中毒蕈碱受体下调。通过[3H]QNB结合测定的分离细胞中毒蕈碱受体密度降低了60 - 65%，而使用[3H]NMS测量的结果则降低了65 - 73%。用梭曼和VX对猪进行7天的亚急性处理导致对卡巴胆碱具有高亲和力的受体比例出现小幅但显著的增加。受体密度的降低伴随着乙酰胆碱诱导的黏液分泌减少。黏液分泌减少并非由于细胞产生或释放黏液的能力下降，因为对甲氧明诱导的黏液分泌并未产生交叉耐受性。因此，我们得出结论，在黏液腺细胞中，耐受性的发展在功能上可能与毒蕈碱受体的丧失有关。
