Angiotensin II type 2 receptor-mediated duodenal mucosal alkaline secretion in the rat

Abstract

The aims of this study were to elucidate the distribution of angiotensin receptors (AT1and AT2) in the duodenal wall and to investigate whether AT2 receptors are involved in the regulation of duodenal mucosal alkaline secretion, which is of importance for the mucosal defense against gastric acid. Immunohistochemistry was used to locate AT1 and AT2 receptors in chloralose-anesthetized rats. Duodenal mucosal alkaline output was measured by use of in situ pH-stat titration. Immunohistochemistry demonstrated a distinct staining for both AT1 and AT2 receptors in the lamina propria of the villi and also for AT1 receptors in the muscularis interna. When angiotensin II was infused in the presence of the AT1receptor antagonist losartan, mucosal alkaline secretion increased by ∼50%. This response was inhibited by the AT2 receptor antagonist PD-123319. The AT2 receptor agonist CGP-42112A increased mucosal alkaline secretion by ∼50%. This increase was absent in the presence of PD-123319 but not in the presence of losartan or the local anesthetic lidocaine. We conclude that angiotensin II stimulates duodenal mucosal alkaline secretion by activation of AT2 receptors located in the duodenal mucosa/submucosa.