The angiotensin II type 2 receptor and the gastrointestinal tract

Abstract

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.

The Effects of Some Neuropeptides on Motor Activity of Smooth Muscle Organs in Abdominal and Pelvic Cavities

“…Local RAS or parts of it had been found in rat rectum , rat small intestine, and in the guinea pig gall bladder (Leung et al, 1993). The role of Ang II had been confirmed in the development of diseases such as the gastro-esophageal reflux (Fändriks, 2010), incontinence of internal anal sphincter Rattan et al, 2003), and Crohn's disease (Fändriks, 2010;Wang et al, 1993) as well as other inflammatory and motility disorders of the GIT (Fändriks, 2010).…”

“…Most of the effects of Ang II concerning the smooth muscle contractile activity of GIT are associated with AT1 receptors (Fändriks, 2010;Fan et al, 2002;Hawcock & Barnes, 1993;Rattan et al, 2003). AT2 receptors are also described in GIT (Fändriks, 2010;Fan et al, 2002;Hawcock & Barnes, 1993;Ewert et al, 2003;Leung et al, 1993;De Godoy et al, 2002).…”

“…AT2 receptors are also described in GIT (Fändriks, 2010;Fan et al, 2002;Hawcock & Barnes, 1993;Ewert et al, 2003;Leung et al, 1993;De Godoy et al, 2002). Although different signaling pathways have been assumed, for example activation of various phosphatases, cGMP -NO system etc.…”

“…(Ewert et al, 2003;Dinh et al, 2001), their actual signal transduction is not quite elucidated. AT2 receptors are associated with the exchange of water and salts, sodium hydrogen carbonate secretion in the duodenum (Fändriks, 2010) and the secretion of nitric oxide in pig's jejunum (Ewert et al, 2003). The significance of AT2 receptors for GIT motility has not been established yet.…”

“…Dosedependent curves, which are commonly used as a method for studying the provoked smooth muscle contractions (Fändriks, 2010;Fan et al, 2002;Hawcock & Barnes, 1993;Leung et al, 1993;Park et al, 1973), could give information about the effective doses and maximal responses, but not a data for other important characteristics of the smooth muscle contractions. The different phases of the contraction in the various segments of the GIT, were not clarified and analyzed by application of a time-parameter analysis, as it was made in the study of the skeletal muscle contraction (Raikova & Aladjov, 2004).…”