-
World Journal of Gastroenterology Oct 2012In the present paper the increasing difficulty of diagnosis of Zollinger-Ellison syndrome (ZES) due to issues raised in two recent papers is discussed. These issues... (Review)
Review
In the present paper the increasing difficulty of diagnosis of Zollinger-Ellison syndrome (ZES) due to issues raised in two recent papers is discussed. These issues involve the difficulty and need to withdraw patients suspected of ZES from treatment with Proton Pump Inhibitors (omeprazole, esomeprazole, lansoprazole, rabeprazole, pantoprazole) and the unreliability of many gastrin radioimmunoassays. The clinical context of each of these important issues is reviewed and the conclusions in these articles commented from the perspective of clinical management.
Topics: Contraindications; Gastrins; Humans; Proton Pump Inhibitors; Zollinger-Ellison Syndrome
PubMed: 23112541
DOI: 10.3748/wjg.v18.i39.5495 -
Acta Bio-medica : Atenei Parmensis Dec 2018The manifestations of gastroesophageal reflux disease (GERD) have been recently classified into either esophageal or extra-esophageal syndromes. Clinical history,... (Review)
Review
The manifestations of gastroesophageal reflux disease (GERD) have been recently classified into either esophageal or extra-esophageal syndromes. Clinical history, questionnaire data and response to antisecretory therapy are insufficient to make a conclusive diagnosis of GERD. Endoscopy had a low sensitivity. Recently, the availability of multichannel intraluminal impedance and pH-monitoring (MII-pH) has modified the diagnostic approach towards atypical manifestations of GERD. There is a rising consensus that this technique should be considered as the gold standard for GERD diagnosis. Gastrin 17 (G-17) has been proposed as a non-invasive marker of GERD, due to the negative feedback between acid and the hormone. G17 levels seem able to identify patients with acid and non-acid reflux.
Topics: Bilirubin; Body Fluids; Chest Pain; Diagnosis, Differential; Electric Impedance; Esophageal pH Monitoring; Gastrins; Gastroesophageal Reflux; Humans; Manometry; Monitoring, Ambulatory; Proton Pump Inhibitors; Symptom Assessment
PubMed: 30561415
DOI: 10.23750/abm.v89i8-S.7963 -
International Journal of Molecular... Jun 2021The antral hormone gastrin potently regulates gastric acid secretion and fundic mucosal growth. Consequently, appropriate gastrin secretion and plasma concentrations are... (Review)
Review
The antral hormone gastrin potently regulates gastric acid secretion and fundic mucosal growth. Consequently, appropriate gastrin secretion and plasma concentrations are important for the early phases of digestion. This review describes as the first premise the normal biogenesis of gastrin in the antral mucosa, but also mentions the extraantral expression. Subsequently, the molecular nature and concentration levels of gastrin in serum or plasma are overviewed. Third, assays for accurate measurements of plasma or serum concentrations are commented. Finally, the problem of moderate hypergastrinemia due to infections and/or treatment with proton-pump inhibitors (PPI) is discussed. The review concludes that accurate measurement of the true concentrations of bioactive gastrins in plasma is important. Moreover, it suggests that moderate hypergastrinemias are also essential health issues that require serious attention.
Topics: Animals; Biomarkers; Disease Susceptibility; Gastric Mucosa; Gastrin-Secreting Cells; Gastrins; Gene Expression Regulation; Helicobacter Infections; Helicobacter pylori; Humans; Molecular Diagnostic Techniques; Organ Specificity; Proton Pump Inhibitors; Reagent Kits, Diagnostic
PubMed: 34209478
DOI: 10.3390/ijms22136977 -
Annals of Surgery Feb 2005Bombesin is an endogenous gut peptide that is prominent in the stomach. In addition to its effects on modulating acid and gut peptide secretion, recent evidence... (Review)
Review
Bombesin is an endogenous gut peptide that is prominent in the stomach. In addition to its effects on modulating acid and gut peptide secretion, recent evidence indicates that bombesin is a potent gastroprotective agent. This review article examines the ability of bombesin to prevent gastric injury. Its protective actions appear to be mediated primarily via the release of endogenous gastrin, as gastroprotection is negated by blockade of gastrin receptors. Bombesin-induced gastroprotection and gastrin release are modified by somatostatin. Immunoneutralization of endogenous somatostatin increases the ability of bombesin to prevent gastric injury by increasing gastrin release. In mechanistic studies, ablation of capsaicin-sensitive afferent neurons abolishes bombesin-induced gastroprotection while cyclo-oxygenase inhibition partially reverses this effect. Nitric oxide synthase inhibition also negates bombesin-induced gastroprotection as well as the ability of bombesin to increase gastric mucosal blood flow. Taken together, the available evidence indicates that bombesin causes release of endogenous gastrin that activates sensory neurons located in the gastric mucosa. Activation of sensory neurons causes increased production of nitric oxide through activation of constitutive nitric oxide synthase, which leads to a resultant increase in gastric mucosal blood flow and renders the stomach less susceptible to damage from luminal irritants.
Topics: Animals; Bombesin; Capsaicin; Cholecystokinin; Cytoprotection; Dose-Response Relationship, Drug; Gastric Mucosa; Gastrins; Humans; Microcirculation; Neurons, Afferent; Nitric Oxide; Nitric Oxide Synthase; Prostaglandins; Regional Blood Flow; Stomach
PubMed: 15650631
DOI: 10.1097/01.sla.0000151790.14274.5d -
Function (Oxford, England) 2022Abetted by widespread usage of acid-suppressing proton pump inhibitors (PPIs), the mitogenic actions of the peptide hormone gastrin are being revisited as a recurring... (Review)
Review
Abetted by widespread usage of acid-suppressing proton pump inhibitors (PPIs), the mitogenic actions of the peptide hormone gastrin are being revisited as a recurring theme in various gastrointestinal (GI) malignancies. While pathological gastrin levels are intricately linked to hyperplasia of enterochromaffin-like cells leading to carcinoid development, the signaling effects exerted by gastrin on distinct cell types of the gastric mucosa are more nuanced. Indeed, mounting evidence suggests dichotomous roles for gastrin in both promoting and suppressing tumorigenesis. Here, we review the major upstream mediators of gastrin gene regulation, including inflammation secondary to infection and the use of PPIs. We further explore the molecular biology of gastrin in GI malignancies, with particular emphasis on the regulation of gastrin in neuroendocrine neoplasms. Finally, we highlight tissue-specific transcriptional targets as an avenue for targetable therapeutics.
Topics: Humans; Gastrins; Helicobacter Infections; Helicobacter pylori; Neoplasm Recurrence, Local; Proton Pump Inhibitors; Gastrointestinal Neoplasms
PubMed: 35330921
DOI: 10.1093/function/zqab062 -
Biomedical Research (Tokyo, Japan) 2023Gastrin and CCK (cholecystokinin), gut hormones first secreted after postprandial stages, share the C-terminal amino acids and some types of receptors to be stimulated.... (Review)
Review
Gastrin and CCK (cholecystokinin), gut hormones first secreted after postprandial stages, share the C-terminal amino acids and some types of receptors to be stimulated. Both types of hormone-secreting cells are typical open-type cells which detect foods and their digested elements in the lumen and regulate the secretion of gastric acid and digestive enzymes, gut motility, and satiety. Gastrin cell granules are characterized by their heterogenous ultrastructure within the cell, while CCK cell granules show a uniform ultrastructural figure. Gastrin cells are equipped with peptone receptor GPR92, amino acid receptor GPRC6A, and a Ca-sensing receptor. In addition to nutrient receptors, the release of CCK is regulated by a unique negative feedback mechanism. Development of an antibody for CCK-specific receptor (CCK-1R) has revealed its exact localization throughout the body, but specific antibodies against CCK-2R remain unavailable. Gastrin affects differentiation and proliferation-including cancer cells, while CCK possesses trophic effects to target tissues. CCK is a peripheral satiety signal and acts either via the vagus or directly on the dorsal medulla via CCK-1R. In this review, endocrine cells secreting these unique and so-called old gut hormones are described on a morphological basis.
Topics: Cholecystokinin; Gastrins; Receptors, Cholecystokinin; Humans
PubMed: 37258205
DOI: 10.2220/biomedres.44.81 -
Frontiers in Endocrinology 2020The structurally-related peptides, gastrin and cholecystokinin (CCK), were originally discovered as humoral stimulants of gastric acid secretion and pancreatic enzyme... (Review)
Review
The structurally-related peptides, gastrin and cholecystokinin (CCK), were originally discovered as humoral stimulants of gastric acid secretion and pancreatic enzyme release, respectively. With the aid of methodological advances in biochemistry, immunochemistry, and molecular biology in the past several decades, our concept of gastrin and CCK as simple gastrointestinal hormones has changed considerably. Extensive and studies have shown that gastrin and CCK play important roles in several cellular processes including maintenance of gastric mucosa and pancreatic islet integrity, neurogenesis, and neoplastic transformation. Indeed, gastrin and CCK, as well as their receptors, are expressed in a variety of tumor cell lines, animal models, and human samples, and might contribute to certain carcinogenesis. In this review, we will briefly introduce the gastrin and CCK system and highlight the effects of gastrin and CCK in the regulation of cell proliferation and apoptosis in both normal and abnormal conditions. The potential imaging and therapeutic use of these peptides and their derivatives are also summarized.
Topics: Animals; Apoptosis; Cell Physiological Phenomena; Cell Proliferation; Cell Transformation, Neoplastic; Cholecystokinin; Gastric Mucosa; Gastrins; Humans; Pancreas; Signal Transduction
PubMed: 32210918
DOI: 10.3389/fendo.2020.00112 -
Current Opinion in Endocrinology,... Feb 2010Chronic infection of the gastric mucosa with Helicobacter pylori has long been recognized as a significant risk factor for gastric cancer, and indeed, this model... (Review)
Review
PURPOSE OF REVIEW
Chronic infection of the gastric mucosa with Helicobacter pylori has long been recognized as a significant risk factor for gastric cancer, and indeed, this model represents the prototypical inflammation-associated cancer. In this review, we present the latest clinical and experimental evidence showing that gastrin peptides and their receptors [the cholecystokinin (CCK2) receptors] potentiate the progression of gastric cancer and other gastrointestinal malignancies in the presence of inflammation.
RECENT FINDINGS
We highlight the feed-forward mechanisms by which gastrin and CCK2 receptor expression are upregulated during inflammation and in gastrointestinal cancers, summarize gastrin's proinflammatory role by inducing the production of cyclooxgenase-2 (COX-2) and interleukin-8 (IL-8), and relate evidence suggesting that gastrin and their receptors modulate the function of immune cells and fibroblasts following cellular stress, injury, repair, as well as during cancer progression.
SUMMARY
We discuss trends for future studies directed toward the elucidation of gastrin peptides' role in regulating intercellular molecular signaling mechanisms between local and circulating immune cells, fibroblasts, epithelial cells, and other cell types in the microenvironments of inflammation-related cancers. Elucidation of the molecular and cellular pathways that relate inflammation with cancer may provide additional opportunities to develop complementary therapies that target the inflammatory microenvironment of the cancer.
Topics: Animals; Cocarcinogenesis; Colorectal Neoplasms; Cytokines; Feedback, Physiological; Gastrins; Gastritis; Gastrointestinal Neoplasms; Helicobacter Infections; Helicobacter pylori; Humans; Inflammation Mediators; Leukocytes; Receptor, Cholecystokinin B
PubMed: 19907321
DOI: 10.1097/MED.0b013e328333faf8 -
International Journal of Biological... 2016The gastrointestinal (GI) peptide gastrin is an important regulator of the release of gastric acid from the stomach parietal cells and it also plays an important role in... (Review)
Review
The gastrointestinal (GI) peptide gastrin is an important regulator of the release of gastric acid from the stomach parietal cells and it also plays an important role in growth of the gastrointestinal tract. It has become apparent that gastrin and its related peptide cholecystokinin (CCK) are also significantly involved with growth of GI cancers as well as other malignancies through activation of the cholecystokinin-B (CCK-B) receptor. Of interest, gastrin is expressed in the embryologic pancreas but not in the adult pancreas; however, gastrin becomes re-expressed in pancreatic cancer where it stimulates growth of this malignancy by an autocrine mechanism. Strategies to down-regulate gastrin or interfere with its interface with the CCK receptor with selective antibodies or receptor antagonists hold promise for the treatment of pancreatic cancer and other gastrin--responsive tumors.
Topics: Animals; Gastrins; Humans; Pancreatic Neoplasms; Receptors, Cholecystokinin
PubMed: 26929735
DOI: 10.7150/ijbs.14952 -
Current Gastroenterology Reports Jul 2017Neuroendocrine tumors (NETs) were initially identified as a separate entity in the early 1900s as a unique malignancy that secretes bioactive amines. GI-NETs are the... (Review)
Review
PURPOSE OF REVIEW
Neuroendocrine tumors (NETs) were initially identified as a separate entity in the early 1900s as a unique malignancy that secretes bioactive amines. GI-NETs are the most frequent type and represent a unique subset of NETs, because at least 75% of these tumors represent gastrin stimulation of the enterochromaffin-like cell located in the body of the stomach. The purpose of this review is to understand the specific role of gastrin in the generation of Gastric NETs (G-NETs).
RECENT FINDINGS
We review here the origin of enterochromaffin cells gut and the role of hypergastrinemia in gastric enteroendocrine tumorigenesis. We describe generation of the first genetically engineered mouse model of gastrin-driven G-NETs that mimics the human phenotype. The common mechanism observed in both the hypergastrinemic mouse model and human carcinoids is translocation of the cyclin-dependent inhibitor p27 to the cytoplasm and its subsequent degradation by the proteasome. Therapies that block degradation of p27, the CCKBR2 gastrin receptor, or gastrin peptide are likely to facilitate treatment.
Topics: Animals; Carcinoid Tumor; Cyclin-Dependent Kinase Inhibitor p27; Cytoplasm; Disease Models, Animal; Enterochromaffin-like Cells; Gastrins; Humans; Mice; Neuroendocrine Tumors; Phenotype; Receptor, Cholecystokinin B; Stomach Neoplasms
PubMed: 28608155
DOI: 10.1007/s11894-017-0572-y