Ghanayem B I, Boor P J, Ahmed A E
J Pharmacol Exp Ther. 1985 Feb;232(2):570-7.
Acrylonitrile [vinyl cyanide (VCN)] induces acute hemorrhagic focal superficial gastric mucosal necrosis or gastric erosions. In this report the authors have studied the mechanism of the VCN-induced gastric erosions. VCN-induced gastric lesions are coupled with a marked decrease of gastric reduced glutathione (GSH) concentration. Pretreatment of rats with various metabolic modulators (cytochrome P-450 monooxygenase and GSH) before VCN demonstrated that there is an inverse and highly significant correlation between gastric GSH concentration and the VCN-induced gastric erosions. Pretreatment of rats with sulfhydryl-containing compounds protected against the VCN-induced gastric necrosis and blocked the VCN-induced gastric GSH depletion. Furthermore, pretreatment of rats with atropine, which blocks muscarinic receptors, protected rats against the VCN-induced gastric erosions. The working hypothesis is that depletion and/or inactivation of critical endogenous sulfhydryl groups causes configurational changes of cholinergic receptors and increases agonist binding affinity, which, among other actions, leads to the causation of gastric mucosal erosions.
丙烯腈[乙烯基氰化物（VCN）]可引发急性出血性局灶性浅表胃黏膜坏死或胃糜烂。在本报告中，作者研究了VCN诱导胃糜烂的机制。VCN诱导的胃部病变与胃内还原型谷胱甘肽（GSH）浓度显著降低相关。在给予VCN之前，用各种代谢调节剂（细胞色素P-450单加氧酶和GSH）对大鼠进行预处理，结果表明胃GSH浓度与VCN诱导的胃糜烂之间存在反向且高度显著的相关性。用含巯基的化合物对大鼠进行预处理可预防VCN诱导的胃坏死，并阻止VCN诱导的胃GSH耗竭。此外，用阿托品（一种阻断毒蕈碱受体的药物）对大鼠进行预处理可保护大鼠免受VCN诱导的胃糜烂。目前的工作假设是，关键内源性巯基的耗竭和/或失活会导致胆碱能受体的构象变化，并增加激动剂结合亲和力，这在其他作用中会导致胃黏膜糜烂的发生。
