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Current Opinion in Gastroenterology Nov 2016The present review summarizes the past year's literature, both clinical and basic science, regarding neuroendocrine and intracellular regulation of gastric acid... (Review)
Review
PURPOSE OF REVIEW
The present review summarizes the past year's literature, both clinical and basic science, regarding neuroendocrine and intracellular regulation of gastric acid secretion and proper use of antisecretory medications.
RECENT FINDINGS
Gastric acid kills microorganisms, modulates the gut microbiome, assists in digestion of protein, and facilitates absorption of iron, calcium, and vitamin B12. The main stimulants of acid secretion are gastrin, released from antral G cells; histamine, released from oxyntic enterochromaffin-like cells; and acetylcholine, released from antral and oxyntic intramural neurons. Other stimulants include ghrelin, motilin, and hydrogen sulfide. The main inhibitor of acid secretion is somatostatin, released from oxyntic and antral D cells. Glucagon-like peptide-1 also inhibits acid secretion. Proton pump inhibitors (PPIs) reduce acid secretion and, as a result, decrease somatostatin and thus stimulate gastrin secretion. Although considered well tolerated drugs, concerns have been raised this past year regarding associations between PPI use and kidney disease, dementia, and myocardial infarction; the quality of evidence, however, is very low.
SUMMARY
Our understanding of the physiology of gastric secretion and proper use of PPIs continues to advance. Such knowledge is crucial for improved management of acid-peptic disorders.
Topics: Chloride Channels; Gastric Acid; Gastric Mucosa; Gastrins; Gastrointestinal Microbiome; Histamine; Humans; Neurosecretory Systems; Potassium Channels; Proton Pump Inhibitors; Somatostatin
PubMed: 27607343
DOI: 10.1097/MOG.0000000000000308 -
Chronobiology International Jun 2020This review concerns the current knowledge of melatonin and alcohol-related disorders. Chronobiological effects of ethanol are related to melatonin suppression and in... (Review)
Review
This review concerns the current knowledge of melatonin and alcohol-related disorders. Chronobiological effects of ethanol are related to melatonin suppression and in relation to inflammation, stress, free radical scavenging, autophagy and cancer risk. It is postulated that both alcohol- and inflammation-induced production of reactive oxygen species (ROS) alters cell membrane properties leading to tissue dysfunction and, subsequent further ROS production. Lysosomal enzymes are often used to assess the relationships between intensified inflammation states caused by alcohol abuse and oxidative stress as well as level of tissue damage estimated by the increased release of cellular enzymes into the extracellular space. Studies have established a link between alcoholism and desynchronosis (circadian disruption). Desynchronosis results from the disorganization of the body's circadian time structure and is an aspect of the pathology of chronic alcohol intoxication. The inflammatory conditions and the activity of lysosomal enzymes in acute alcohol poisoning or chronic alcohol-dependent diseases are in most cases interrelated. Inflammation can increase the activity of lysosomal enzymes, which can be regarded as a marker of lysosomal dysfunction and abnormal cellular integrity. Studies show alcohol toxicity is modulated by the melatonin (Mel) circadian rhythm. This hormone, produced by the pineal gland, is the main regulator of 24 h (sleep-wake cycle) and seasonal biorhythms. Mel exhibits antioxidant properties and may be useful in the prevention of oxidative stress reactions known to be responsible for alcohol-related diseases. Naturally produced Mel and exogenous sources in food can act in free radical reactions and activate the endogenous defense system. Mel plays an important role in the normalization of the post-stress state by its influence on neurotransmitter systems and the synchronization of circadian rhythms. Acting simultaneously on the neuroendocrine and immune systems, Mel optimizes homeostasis and provides protection against stress. ROS, reactive oxygen species; Mel, melatonin; SRV, resveratrol; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; ANT, arylalkylamine-N-acetyltransferase; EC cells, gastrointestinal enterochromaffin cells; MT1, melatonin high-affinity nanomolecular receptor site; MT2, melatonin low-affinity nanomolecular receptor site; ROR/RZR, orphan nuclear retinoid receptors; SOD, superoxide dismutase; CAT, catalase; GPx, glutathione peroxidase; GR, glutathione reductase; GSH, reduced form of glutathione; GSSG, oxidized form of glutathione; TAC, total antioxidant capacity; ONOO∙, peroxynitrite radical; NCAM, neural cell adhesion molecules; LPO, lipid peroxidation; α-KG, α-ketoglutarate, HIF-1α, Hypoxia-inducible factor 1, IL-2, interleukin-2; HPA axis, hypothalamic-pituitary-adrenal axis; Tph1, tryptophan hydroxylase 1; AA-NAT, arylalkylamine-N-acetyltransferase; AS-MT, acetylserotonin O-methyltransferase; NAG, N-acetyl-beta-D-glucosaminidase; HBA1c glycated hemoglobin; LPS, lipopolysaccharide; AAP, alanyl-aminopeptidase; β-GR, β-glucuronidase; β-GD, β-galactosidase; LAP, leucine aminopeptidase.
Topics: Alcohol-Related Disorders; Antioxidants; Circadian Rhythm; Humans; Hypothalamo-Hypophyseal System; Melatonin; Oxidative Stress; Pituitary-Adrenal System; Superoxide Dismutase
PubMed: 32419511
DOI: 10.1080/07420528.2020.1761372 -
Scandinavian Journal of Gastroenterology Jun 2020Studies on the regulation of gastric acid secretion started more than 100 years ago at an early phase of experimental physiology. In nearly the whole last century there... (Review)
Review
Studies on the regulation of gastric acid secretion started more than 100 years ago at an early phase of experimental physiology. In nearly the whole last century there were disputes about the interpretation of the findings: the interaction between the three principle gastric acid secretagogues acetylcholine, gastrin and histamine, the cell producing the relevant histamine which turned out to be the ECL cell, the ability of the ECL cell to divide and thus develop into tumours, the classification of gastric carcinomas and the mechanism for Helicobacter pylori carcinogenesis. The elucidation of the central role of the ECL cell and thus its main regulator, gastrin, solve all these controversies, and gives a solid base for handling upper gastrointestinal diseases.
Topics: Animals; Carcinogenesis; Enterochromaffin-like Cells; Gastric Acid; Gastric Mucosa; Gastrins; Helicobacter pylori; Humans; Stomach Neoplasms
PubMed: 32515242
DOI: 10.1080/00365521.2020.1771758 -
World Journal of Clinical Cases Sep 2021Gastric neuroendocrine neoplasms (g-NENs) or neuroendocrine tumors are generally slow-growing tumors with increasing incidence. They arise from enterochromaffin like... (Review)
Review
Gastric neuroendocrine neoplasms (g-NENs) or neuroendocrine tumors are generally slow-growing tumors with increasing incidence. They arise from enterochromaffin like cells and are divided into four types according to clinical characteristic features. Type 1 and 2 are gastrin dependent, whereas type 3 and 4 are sporadic. The reason for hypergastrinemia is atrophic gastritis in type 1, and gastrin releasing tumor (gastrinoma) in type 2 g-NEN. The diagnosis of g-NENs needs histopathological investigation taken by upper gastrointestinal endoscopy. g-NENs are positively stained with chomogranin A and synaptophysin. Grading is made with mitotic index and ki-67 proliferation index on histopathological analysis. It is crucial to discriminate between types of g-NENs, because the management, treatment and prognosis differ significantly between subtypes. Treatment options for g-NENs include endoscopic resection, surgical resection with or without antrectomy, medical treatment with somatostatin analogues, netazepide or chemotherapy regimens. Follow-up without excision is another option in appropriate cases. The prognosis of type 1 and 2 g-NENs are good, whereas the prognosis of type 3 and 4 g-NENs are close to the prognosis of gastric adenocancer.
PubMed: 34621854
DOI: 10.12998/wjcc.v9.i27.7973 -
Pharmacological Research Feb 2019A large number of studies have focused on the role of serotonin as a neurotransmitter in the central nervous system, although only a small percentage of the body's... (Review)
Review
A large number of studies have focused on the role of serotonin as a neurotransmitter in the central nervous system, although only a small percentage of the body's serotonin (∼5%) can be found in the mature brain of mammals. In the gut, the enterochromaffin cells are scattered in the enteric epithelium from the stomach through the colon and produce over 95% of the body's serotonin. Since the generation of tryptophan hydroxylase (Tph1 and Tph2) knockout mice, unsuspected roles have been identified for serotonin synthesized outside the brain. Moreover, the murine model deficient in peripheral serotonin (Tph1) is a unique experimental tool for exploring the molecular and cellular mechanisms involving serotonin's local effects through microserotonergic systems. In this review, we focus on peripheral serotonin and its role on progenitor or stem cells as well as on hematopoietic progenitors. We discuss the possible role of serotonin in hematopoietic diseases, and whether targeting the serotonergic system could be of therapeutic value for the regulation of normal and pathological hematopoiesis.
Topics: Animals; Embryonic Development; Hematopoiesis; Humans; Serotonin; Selective Serotonin Reuptake Inhibitors; Stem Cells
PubMed: 30107202
DOI: 10.1016/j.phrs.2018.08.005 -
Frontiers in Physiology 2022Mechanosensation is essential for normal gastrointestinal (GI) function, and abnormalities in mechanosensation are associated with GI disorders. There are several... (Review)
Review
Mechanosensation is essential for normal gastrointestinal (GI) function, and abnormalities in mechanosensation are associated with GI disorders. There are several mechanosensitive ion channels in the GI tract, namely transient receptor potential (TRP) channels, Piezo channels, two-pore domain potassium (K2p) channels, voltage-gated ion channels, large-conductance Ca-activated K (BKCa) channels, and the cystic fibrosis transmembrane conductance regulator (CFTR). These channels are located in many mechanosensitive intestinal cell types, namely enterochromaffin (EC) cells, interstitial cells of Cajal (ICCs), smooth muscle cells (SMCs), and intrinsic and extrinsic enteric neurons. In these cells, mechanosensitive ion channels can alter transmembrane ion currents in response to mechanical forces, through a process known as mechanoelectrical coupling. Furthermore, mechanosensitive ion channels are often associated with a variety of GI tract disorders, including irritable bowel syndrome (IBS) and GI tumors. Mechanosensitive ion channels could therefore provide a new perspective for the treatment of GI diseases. This review aims to highlight recent research advances regarding the function of mechanosensitive ion channels in the GI tract. Moreover, it outlines the potential role of mechanosensitive ion channels in related diseases, while describing the current understanding of interactions between the GI tract and mechanosensitive ion channels.
PubMed: 36060694
DOI: 10.3389/fphys.2022.904203 -
Annals of Surgical Oncology Mar 2024Gastric neuroendocrine tumors (G-NET) are rare tumors arising from enterochromaffin-like cells of the gastric mucosa. They belong to a larger group called... (Review)
Review
Gastric neuroendocrine tumors (G-NET) are rare tumors arising from enterochromaffin-like cells of the gastric mucosa. They belong to a larger group called gastroenteropancreatic neuroendocrine tumors and are classified as low, intermediate, or high-grade tumors based on their proliferative indices. They are further categorized into three subtypes based on their morphologic characteristics, pathogenesis, and behavior. Types 1 and 2 tumors are characterized by elevated serum gastrin and are usually multifocal. They typically occur in the setting of atrophic gastritis or MEN1/Zollinger Ellison syndrome, respectively. Type 2 tumors are associated with the most symptoms, such as abdominal pain and diarrhea. Type 3 tumors are associated with normal serum gastrin, are usually solitary, and occur sporadically. This type has the most aggressive phenotype and metastatic potential. Treatment and prognosis for G-NET is dependent on their type, size, and stage. Type 1 has the best prognosis, and Type 3 has the worst. This review discusses the presentation, workup, and surgical management of these tumors.
Topics: Humans; Gastrins; Neuroendocrine Tumors; Zollinger-Ellison Syndrome; Pancreatic Neoplasms; Gastric Mucosa; Stomach Neoplasms
PubMed: 38062290
DOI: 10.1245/s10434-023-14712-9 -
Neurogastroenterology and Motility Feb 2018Tryptophan is an important dietary amino acid and it is the precursor for 5-hydroxytryptamine synthesis in the nervous system and by enterochromaffin cells in the gut... (Review)
Review
Tryptophan is an important dietary amino acid and it is the precursor for 5-hydroxytryptamine synthesis in the nervous system and by enterochromaffin cells in the gut mucosa. Tryptophan is also metabolized by enzymes in the gut mucosa and also by enzymes produced by the gut microbiome. Diet and the microbiome can contribute to metabolic disease in part by causing intestinal inflammation and increased permeability. In this issue of Neurogastroenterology and Motility, Jennis et al. test the hypothesis that indole tryptophan metabolites produced by gut bacteria might be responsible for the anti-inflammatory and beneficial metabolic effects of the gut microbiome and Roux-en-Y gastric bypass surgery for weight loss by obese patients. The authors identified indole-3-propionic acid as the beneficial metabolite. A review of the literature also revealed the beneficial effects of tryptophan metabolites on diabetes and metabolic disease and on inflammatory bowel disease. Taken together, these data highlight another health benefit of the intestinal microbiome, which produces beneficial products from dietary amino acids especially tryptophan.
Topics: Diabetes Mellitus, Type 2; Gastrointestinal Microbiome; Humans; Obesity; Tryptophan
PubMed: 29341448
DOI: 10.1111/nmo.13283 -
Biochimie Jun 2019Serotonin (5-hydroxytryptamine or 5-HT) once most extensively studied as a neurotransmitter of the central nervous system, is seen to be predominantly secreted in the... (Review)
Review
Serotonin (5-hydroxytryptamine or 5-HT) once most extensively studied as a neurotransmitter of the central nervous system, is seen to be predominantly secreted in the gut. About 95% of 5-HT is estimated to be found in gut mainly within the enterochromaffin cells whereas about 5% is found in the brain. 5-HT is an important enteric signaling molecule and is well known for playing a key role in sensory-motor and secretory functions in the gut. In recent times, studies uncovering various new functions of gut-derived 5-HT indicate that many more are yet to be discovered in coming days. Recent studies revealed that 5-HT plays a pivotal role in immune cell activation and generation/perpetuation of inflammation in the gut. In addition to its various roles in the gut, there are now emerging evidences that suggest an important role of gut-derived 5-HT in other biological processes beyond the gut, such as bone remodeling and metabolic homeostasis. This review focuses to briefly summarize the accumulated and newly updated role of 5-HT in the maintenance of normal gut physiology and in the pathogenesis of inflammation in the gut. The collected information about this multifaceted signaling molecule may aid in distinguishing its good and bad effects which may lead to the development of novel strategies to overcome the unwanted effect, such as in inflammatory bowel disease.
Topics: Animals; Gastrointestinal Tract; Humans; Inflammation; Receptors, Serotonin; Serotonin
PubMed: 29909048
DOI: 10.1016/j.biochi.2018.06.008 -
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