The mechanistic pathway of gastric adaptive cytoprotection: a study on different components of the autonomic nervous...

1. The involvement of different components of the autonomic nervous system in the pathogenesis of ethanol-induced damage and the adaptive cytoprotection of mild irritants were studied in the gastric mucosa of male rats. 2. Capsaicin, yohimbine, and domperidone aggravated the 100% ethanol-induced gastric mucosal damage and attenuated the cytoprotective action of 20% ethanol, but not of 5% NaCl and 0.3 M HCl. Butoxamine and prazosin blocked the adverse actions of yohimbine and domperidone respectively. 3. Atropine, pirenzepine, and lidocaine lessened the severity of 100% ethanol-induced mucosal injury and further increased the cytoprotective action of 5% NaCl and 0.3 M HCl, but not of 20% ethanol. 4. Our results demonstrated that sensory afferent neurones, alpha 2-adrenoceptors and D2-dopaminergic receptors all play a significant role in the defensive mechanism of the gastric mucosa and the adaptive cytoprotection of 20% ethanol, while the M1- and M2-muscarinic receptors and sensory chemoreceptors on the gastric mucosa contribute only to the former action. The adverse effect of yohimbine and domperidone on lesion formation is probably mediated through the release of catecholamines, which subsequently act on the beta 2- and alpha 1-adrenoceptors respectively.