Gastrin: old hormone, new functions

Abstract

It is exactly a century since the gastric hormone gastrin was first described as a blood-borne regulator of gastric acid secretion. The identities of the main active forms of the hormone (the "classical gastrins") and their cellular and molecular sites of action in regulating acid secretion have all attracted sustained attention. However, recent work on peptides derived from the gastrin precursor that do not stimulate acid secretion ("non-classical gastrins"), together with studies on mice over-expressing the gene, or in which the gastrin gene has been deleted, suggest hitherto unsuspected roles in regulating cell proliferation, migration, and differentiation. Moreover, microarray and proteomic studies have identified previously unsuspected target genes of the classical gastrins. Some of the newer actions have implications for our understanding of the progression to cancer in oesophagus, stomach, pancreas and colon, all of which have recently been linked in one way or another to dysfunctional signalling involving products of the gastrin gene. The present review focuses on recent progress in understanding the biology of both classical and non-classical gastrins.

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

“…It is known that the cholecystokinin receptor has 2 subtypes, type 1 and type 2. The expression of CCK2R (CCKBR) is greater than CCK1R in both myocardium and coronary artery10 and has a 500‐ to 1000‐fold higher affinity for gastrin than CCK1R 25, 26. In the present study, the protective effect of gastrin was abolished in the presence of a CCK2R inhibitor, CI988 (Figure 7A–7E).…”

“…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 a 500‐ to 1000‐fold higher affinity for CCK2R than CCK1R 25, 26. CCK2R is highly expressed not only in the stomach and the gastrointestinal tract but also in the heart, brain, and kidney 8, 10, 41.…”

Pancreatic adenocarcinoma patients with localised chronic severe pancreatitis show an increased number of single beta cells, without alterations in fractional insulin area

“…Gastrin is a potent growth factor for the entire gastrointestinal tract and is produced in fetal islet cells [29,30]. Excessive serum gastrin levels could produce profound growth effects on cell types expressing gastrin receptors, including pancreatic ductular epithelium and acinar cells [25,31]. To address our hypothesis that beta cell replication would be observed in non-autoimmune human pancreatic disorders with chronic pancreatitis and localised inflammation or elevated gastrin levels, we performed a series of studies assessing the fractional insulin area as a marker of beta cell mass, followed by detailed analysis of beta cell numbers and replication rates with three different pancreatic distribution patterns.…”

Identification of novel growth factor-responsive genes in neuroendocrine gastrointestinal tumour cells

“…The amidated form of the peptide hormone gastrin is a wellknown regulator of gastric acid secretion and GI mucosal growth and organisation (Waldum et al, 1995;Dockray et al, 2001Dockray et al, , 2005. In addition, there is abundant evidence to suggest that gastrin may play an important role in tumour biology, as it is shown to regulate tumour cell growth (Dockray et al, 2001(Dockray et al, , 2005, and stimulate tumour cell invasion (Kucharczak et al, 2001) as well.…”