The angiotensin II type 2 receptor and the gastrointestinal tract

The renin-angiotensin system (RAS) is well known for its vital involvement in body fluid homeostasis and circulation. However, very little research has been devoted to the impact of this regulatory system on the gastrointestinal (GI) system. This is surprising because the GI tract is fundamental for the intake and excretion of fluid and electrolytes (and nutrients), and it accommodates a large proportion of bodily haemodynamics and host defence systems. The RAS is well expressed and active in the GI tract, although the exact roles for the key mediator angiotensin II (Ang II) and its receptors in general, and the type 2 (AT(2)) receptor in particular, are not completely settled. There are several reports showing Ang II regulation of intestinal fluid and electrolyte transport. For example, mucosaprotective duodenal bicarbonate-rich secretion is inhibited by Ang II via type 1 (AT(1)) receptor-mediated facilitation of sympathoadrenergic activity, but this secretory process can also be stimulated by Ang II via AT(2) receptors. Novel data from human oesophagus and jejunum suggest that the AT(1) receptor mediates muscular contractions and that the AT(2) receptor regulates epithelial functions. Data are accumulating suggesting involvement of AT(1) and AT(2) receptors in GI inflammation and carcinogenesis. The picture of the RAS and AT(2) receptor in the GI tract is, however, far from complete. Much more basic research is needed with regard to GI pathophysiology before concluding clinical significance and potential applicability of pharmacological interferences with the RAS.