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 (AT(1) and AT(2)) in the duodenal wall and to investigate whether AT(2) 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 AT(1) and AT(2) 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 AT(1) and AT(2) receptors in the lamina propria of the villi and also for AT(1) receptors in the muscularis interna. When angiotensin II was infused in the presence of the AT(1) receptor antagonist losartan, mucosal alkaline secretion increased by ~50%. This response was inhibited by the AT(2) receptor antagonist PD-123319. The AT(2) 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 AT(2) receptors located in the duodenal mucosa/submucosa.

A Modern Understanding of the Traditional and Nontraditional Biological Functions of Angiotensin-Converting Enzyme

“…Small intestine Increases bicarbonate secretion (Johansson et al, 2001) and sodium and water retention, directly or through stimulation of sympathetic nervous system (Levens et al, 1981;Garg et al, 2012).…”

The angiotensin II type 2 receptor and the gastrointestinal tract

“…10 Ang II alone had no effects on baseline secretion, but induced surprisingly a marked secretory response if given together with a AT 1 receptor antagonist. 11 That unexpected secretory response was sensitive to compound PD123319, indicating the existence of an AT 2 receptor-mediated activation of DMBS. Immunohistochemistry demonstrated a distinct staining for AT 2 receptors in the lamina propria of duodenal villi.…”

An angiotensin II receptor antagonist reduces inflammatory parameters in two models of colitis

“…Moreover, Ang II is known to regulate motility in the intestine, as well as ion and water absorption via receptors in the mucosa and muscle [11]. Colonic mucosal levels of both angiotensin I and II are greater in patients with Crohn's disease, and appear to correlate with the degree of inflammation [12].…”