Novel roles of gastrin

Abstract

The existence of the hormone gastrin in the distal stomach (antrum) has been known for almost 110 years, and the physiological function of this amidated peptide in regulating gastric acid secretion via the CCK2 receptor is now well established. In this brief review we consider important additional roles of gastrin, including regulation of genes encoding proteins such as plasminogen activator inhibitors and matrix metalloproteinases that have important actions on extracellular matrix remodelling. These actions are, at least in part, effected by paracrine signalling pathways and make important contributions to maintaining functional integrity of the gastric epithelium. Recent studies also provide support for the idea that gastrin, in concert with other hormones, could potentially contribute a post-prandial incretin effect. We also review recent developments in the biology of other gastrin gene products, including the precursor progastrin, which causes proliferation of the colonic epithelium and in certain circumstances may induce cancer formation. Glycine-extended biosynthetic processing intermediates also have proliferative effects in colonic mucosa and in some oesophageal cancer cell lines. Whether these additional gene products exert their effects through the CCK2 receptor or a separate entity is currently a matter of debate.

Gastrin Protects Against Myocardial Ischemia/Reperfusion Injury via Activation of RISK (Reperfusion Injury Salvage Kinase) and SAFE (Survivor Activating Factor Enhancement) Pathways

“…That the physiological function of gastrin in regulating gastric acid secretion occurs via the CCK2R is now well established 25, 34. In recent years, however, several lines of evidence have emerged to suggest that there is much more to the biology of gastrin than is indicated by earlier work 25, 35. Gastrin has been shown to display proliferative,36, 37 antiapoptotic,38 and cell migration39 properties.…”

The stomach in health and disease

“…Recent evidence suggests that gastrin also regulates other important cellular pathways in the stomach including cell proliferation, migration, invasion, angiogenesis and apoptosis (recently reviewed in ref. 21) and a recent in vitro study showed that gastrin plays a key role in maintaining gastric stem cells. 22 Some of these effects arise as a result of the altered expression of proteins that regulate tissue remodelling including members of the matrix metalloproteinase, 23 tissue inhibitor of metalloproteinase 24 and urokinase plasminogen activator 25 families.…”

Obesity and related risk factors in gastric cardia adenocarcinoma

“…Nevertheless, the results are provocative and consistent with another study [38] showing a weak association between acid-suppressing medication use and total number of gastric cancer cases, not broken down by anatomical subsite. A mechanistic link between the use of these medications and gastric carcinogenesis is conceivable, on the basis of the moderately elevated gastrin levels frequently found in users of these drugs and the trophic (proproliferative) effects of gastrin on the gastrointestinal mucosa [39].…”