Gastrin Secretion Research Articles

Transcriptional and Functional Characterization of the G Protein-Coupled Receptor Repertoire of Gastric Somatostatin Cells.

In the stomach, somatostatin (SST) acts as a general paracrine negative regulator of exocrine secretion of gastric acid and pepsinogen and endocrine secretion of gastrin, ghrelin, and histamine. Using reporter mice expressing red fluorescent protein (RFP) under control of the SST promotor, we have characterized the G protein-coupled receptors expressed in gastric Sst-RFP-positive cells and probed their effects on SST secretion in primary cell cultures. Surprisingly, besides SST, amylin and PYY were also highly enriched in the SST cells. Several receptors found to regulate SST secretion were highly expressed and/or enriched. 1) The metabolite receptors calcium-sensing receptor and free fatty acid receptor 4 (GPR120) functioned as positive and negative regulators, respectively. 2) Among the neurotransmitter receptors, adrenergic receptors α1a, α2a, α2b, and β1 were all highly expressed, with norepinephrine and isoproterenol acting as positive regulators. The muscarinic receptor M3 acted as a positive regulator, whereas M4 was conceivably a negative regulator. 3) Of the hormone receptors, the GLP-1 and GIP receptors, CCKb (stimulated by both CCK and gastrin) and surprisingly the melanocortin MC1 receptor were all positive regulators. 4) The neuropeptide receptors for calcitonin gene-related peptide, adrenomedullin, and vasoactive intestinal peptide acted as positive regulators, no effect was observed using galanin and nociceptin although transcripts for the corresponding receptors appeared highly expressed. 5) The SST receptors 1 and 2 functioned in an autocrine negative feedback loop. Thus, the article provides a comprehensive map of receptors through which SST secretion is regulated by hormones, neurotransmitters, neuropeptides and metabolites that act directly on the SST cells in the gastric mucosa.

Toll-Like Receptor 4 Wild Type Homozygozity of Polymorphisms +896 and +1196 Is Associated with High Gastrin Serum Levels and Peptic Ulcer Risk.

Toll-like receptor 4 is a part of the innate immune system and recognizes Helicobacter pylori lipopolysaccharide. The goal of this study was to analyze the role of Toll-like receptor 4 polymorphisms +896 (rs4986790) and +1196 (rs4986791) in the pathogenesis of Helicobacter pylori related gastroduodenal diseases in relation to gastric secretion and inflammation. Toll-like receptor 4 polymorphisms, serum gastrin-17 and pepsinogen I and II concentrations were determined, and gastroscopies with histopathological analyses were performed to 216 dyspeptic patients. As genotype controls, 179 controls and 61 gastric cancer patients were studied. In our study, the Toll-like receptor 4 +896 and +1196 polymorphisms were in total linkage disequilibrium. The homozygous wild types displayed higher gastrin-17 serum concentrations than the mutants (p = 0.001) and this effect was independent of Helicobacter pylori. The homozygous wild types also displayed an increased risk for peptic ulcers (OR: 4.390). Toll-like receptor 4 genotypes did not show any association with Helicobacter pylori positivity or the features of gastric inflammation. Toll-like receptor 4 expression was seen in gastrin and somatostatin expressing cells of antral mucosa by immunohistochemistry. Our results suggest a role for Toll-like receptor 4 in gastric acid regulation and that the Toll-like receptor 4 +896 and +1196 wild type homozygozity increases peptic ulcer risk via gastrin secretion.

Effects of different routes of nicotine administration on gastric morphology and hormonal secretion in rats

What is the central question of this study? Does chronic administration of nicotine by different routes affect gastric hormonal secretions and morphology in rats? What is the main finding and its importance? Chronic nicotine administration increased levels of gastrin, ghrelin and histamine but decreased prostaglandinE2 . Nicotine administered orally and by inhalation had a marked negative impact on the histological structure of the gastric mucosa compared with intraperitoneal administration. The negative impact of nicotine administration on gastric structure was associated with an increased concentration of gastrin and decreased prostaglandinE2 , which might be the cause of gastric/peptic ulcers in heavy smokers. The increase in ghrelin concentration and its effect following chronic nicotine administration needs further investigation. The aim was to assess the effects of different routes of chronic nicotine administration on gastric morphology and hormonal secretion; mainly gastrin, ghrelin, histamine and prostaglandinE2 (PGE2 ). Forty adult male albino rats were randomly assigned into four groups (10rats per group), treated for 21 days as follows: control group (given standard rat pellets and water only); oral nicotine-treated group [50μg(ml drinking water)(-1) ]; intraperitoneal nicotine-treated group [0.5mg(kg body weight)(-1) ]; and inhaled nicotine-treated group [0.5mg(kg body weight)(-1) ]. Concentrations of gastrin, ghrelin, PGE2 and histamine in serum and gastric tissue homogenates were assessed using ELISA kits. Stomach fundus was processed for histopathology and immunohistochemistry using light and electron microscopy. Different routes of chronic nicotine administration resulted in a significant increase in serum and gastric homogenate gastrin and ghrelin concentrations and a significant decrease in serum and homogenate PGE2 concentrations compared with the control group. Moreover, nicotine administration via oral and inhalation routes caused gastric erosion, transformation of peptic cells into the mucous variety, a significant increase in parietal cell numbers and an increase in expression of gastrin. In conclusion, the negative impact of nicotine administration on gastric structure that is associated with an increased concentration of gastrin and decreased concentration PGE2 might be the leading cause of gastric/peptic ulcers in heavy smokers. The increased ghrelin concentration and its effect following nicotine chronic administration needs further investigation. Based on these findings, we suggest that the alteration in gastric structure following chronic administration of nicotine can be prevented by reducing gastrin secretion and/or targeting its receptors.

Biochemical Testing in Patients with Neuroendocrine Tumors.

Neuroendocrine tumors are usually slow-growing tumors. Many of these are capable of secreting peptide hormones or biogenic amines that may lead to endocrine syndromes. Nonfunctioning tumors can either secrete no hormones at all, or secrete hormones not giving rise to endocrine symptoms, such as chromogranin A, chromogranin B or pancreatic polypeptide. Chromogranin A is produced by the majority of endocrine tumors, both functioning and nonfunctioning, and is the best available marker for diagnosis, follow-up and treatment monitoring of patients with differentiated neuroendocrine tumors. Examples of endocrine syndromes are classical carcinoid syndrome caused by serotonin (measured in the urine as its metabolite 5-HIAA), insulinoma syndrome caused by insulin or proinsulin, Zollinger-Ellison syndrome resulting from gastrin secretion, glucagonoma syndrome caused by glucagon, WDHA syndrome caused by vasoactive intestinal peptide, or Cushing's syndrome resulting from ectopic production of adrenocorticotropic hormone or corticotropin-releasing hormone. In case there is uncertainty about the diagnosis, specific tests can be applied, such as the secretin test for diagnosis of gastrinomas and the 72-hour fast for diagnosis of an insulinoma. In patients with suspicion of an inherited syndrome, such as multiple endocrine neoplasia (MEN) 1 and MEN2 syndromes, genetic testing is indicated.

Acupuncture for Functional Dyspepsia: A Single Blinded, Randomized, Controlled Trial.

In order to investigate the therapeutic potential of acupuncture on patients with functional dyspepsia (FD), patients were randomized to receive acupuncture at classic acupoints with manipulations (treatment group) versus acupuncture at nonacupoints without manipulation (control group) once every other day, three times a week, for one month and were followed up for three months. The primary outcomes included dyspeptic symptoms, quality of life, and mental status. The secondary outcomes included the fasting serum gastrin concentration, and frequency and propagation velocity of gastric slow waves. Sixty patients with FD were included, among whom, four dropped out. After one month's treatment, patients with FD showed significant improvements in primary (in both groups) and secondary (in the eight patients of the treatment group) outcomes as compared with baseline (P = 0.0078 to <0.0001); treatment group has better outcomes in all primary outcome measures (P < 0.0001 except for SDS (P = 0.0005)). Improvements on dyspeptic symptoms persist during follow-up (better in the treatment group). Acupuncture with manual manipulation had better effects on improving dyspeptic symptoms, mental status, and quality of life in patients with FD. These effects may be related to the increased frequency and propagation speed of gastric slow waves and serum gastrin secretion.

Prevalence of benign gastric polyps in a large pathology database

AimsThe aim of the study was to utilize a large national histopathology database for the analysis of the clinical epidemiology of gastric polyps. MethodsIn a case–control study, 71,575 case subjects with gastric polyps were compared to 741,351 control subjects without gastric polyps. ResultsOf all patients, 7.72% harboured fundic gland polyps, 1.79% gastric hyperplastic polyps, 0.09% gastric adenomas, and 0.06% type I neuroendocrine tumours. All types showed a clear-cut age-dependent rise. Reflux disease was significantly more common in patients with fundic gland polyps and significantly less common in patients with gastric adenomas or neuroendocrine tumours. Anaemia was more common in patients with gastric hyperplastic polyps, gastric adenomas, or neuroendocrine tumours. Helicobacter pylori was found significantly less frequently in all subjects with gastric polyps than in controls. Intestinal metaplasia and gastric atrophy were both more common in gastric adenoma and neuroendocrine tumours and less common in fundic gland polyps than in controls. Different polyp types tended to coincide in the same patients. ConclusionsGastric hyperplastic polyps appeared to mark the beginning of a progression from chronic gastritis to intestinal metaplasia and gastric atrophy, which leads to diminished gastric acid output and increased gastrin secretion. Gastric adenoma and neuroendocrine tumours reflect later stages of this process.

Sympathetic regulation of estradiol secretion from the ovary.

It is well known that hormone secretion from endocrine glands is regulated by hierarchical feedback mechanisms. However, although Cannon revealed in the 1920s that sympathoadrenal medullary function increased during emergency situations, no studies on the autonomic nervous regulation of hormone secretion have been undertaken for many years. In the past 40 years, the autonomic nervous regulation of insulin secretion from the pancreas, gastrin secretion from the stomach, glucocorticoid secretion from the adrenal cortex, etc., has been demonstrated. Estradiol secretion from the ovary is strongly controlled by the hypothalamic-pituitary-ovarian axis, and its possible regulation by autonomic nerves has been largely unnoticed. Some histological studies have revealed rich adrenergic sympathetic innervation in the ovary. Recently, it has been demonstrated that the activation of the sympathetic nerves to the ovary directly reduces estradiol secretion from the ovary. This article reviews physiological and morphological studies, primarily in rats, on the sympathetic regulation of estradiol secretion from the ovary.

A review of the receptor binding and pharmacological effects of N-methyltyramine.

N-methyltyramine (NMT) is a protoalkaloid isolated from various plant species. It is assumed that NMT is an adrenergic agonist with pharmacological properties similar to other structurally related biogenic amines. Current research studies indicate that NMT is an α-adrenoreceptor antagonist, and exhibits modest inhibitory (antagonistic) activity with respect to the breakdown of fats (lipolysis). Furthermore, NMT has been shown to enhance appetite and digestion of foods through its stimulatory effects on gastrin and pancreatic secretions. As a consequence, NMT is not an ingredient that should be used in dietary supplements designed to promote weight loss. It may result in an increase in perceived energy by promoting appetite and the digestion and absorption of nutrients while inhibiting the breakdown to fats to energy.

Abstract 516: Intestinal Cell Gastrin Secretion is Regulated by a Sodium-Induced Increase in PPAR-A that is Mediated by Dopaminergic Stimulation

Recently a novel gastro-renal axis has been discovered for the regulation of renal sodium excretion at the moment of sodium ingestion. Cells in the digestive track secrete gastrin in response to sodium ingestion which stimulates an increase in renal sodium excretion. Dopamine is largely responsible for the regulation of sodium excretion in the kidney, and has also been shown to decrease sodium transport in intestines. We hypothesized that dopamine might also be involved with the regulation of gastrin secretion in a human intestinal gastrin secreting cell line (SW626, ATCC, Manassas VA) that also contains dopaminergic receptors. We used the ionophore monensin (MON) to increase intracellular sodium in SW626 cells in order to simulate an oral sodium load. We also stimulated the cells with the dopaminergic agonist SKF38393 (SKF, D 1 -like receptor agonist). These two manipulations (compared to vehicle VEH) caused increased relative gene expression of gastrin (ΔΔCt gastrin to actin, VEH 0.00638±0.00283; MON 0.3913372±0.0985926; SKF 0.2139286±0.0253672; P&lt;0.01 VEH vs MON or SKF, N=6 per group). Peroxisome proliferator-activated receptor-alpha (PPAR-α) associates with the gastrin transcriptional promoter by CHIP-SEQ (ENCODE database) and PPAR-α activation by fenofibrate (FENO) has been shown to reduce blood pressure and increase sodium excretion. We hypothesized that PPAR alpha would increase gastrin expression. FENO increased the immunoreactive gastrin and this effect was blocked by a PPAR alpha antagonist GW6471 (VEH 16,440±2,438 RFU; FENO 42,639±4,891; FENO+GW 19,367±1,865; P&lt;0.001 VEH vs FENO and FENO vs FENO+GW). Stimulation with MON or SKF also significantly stimulated the production of immunoreactive gastrin (VEH 16,440±2,438 RFU; MON 22,345±935; SKF 24,386±1,124; GW alone 10,235±1,214; P&lt;0.05 VEH vs MON, SKF, or GW, N=6). SW626 appear to secrete gastrin, therefore we tested the ability of secreted gastrin obtained from the media bathing SW626 cells to bind to i22 human renal proximal tubule cells (RPTC). After incubation of i22 RPTC in SW626 media for 24 hours, we detected surface gastrin staining on the i22 RPTC. We conclude that gastrin is produced by SW626 cells, is secreted into the growth media, and can bind to cell surface receptors on RPTC.

Inhibitory Effects of Deoxynivalenol on Gastric Secretion in Rats

Deoxynivalenol (DON) is a common mycotoxin produced by Fusarium sp. in cereals and foods. Ingestion of contaminated foodstuffs can cause digestive disorders in various animals. Many researchers focus on its toxicity and the pathological damage and absorptive function in the intestines. However, the effect of DON on gastric function is still unclear. The objective of the current study was to evaluate the impact of DON on gastric secretion. Rats were gavaged with DON at the dose of 0, 1, 5, and 25 mg/kg of body weight (bw). Gastric fluids were gathered by pylorus ligation 0.5 h after DON exposure. The results indicate that the volume of gastric fluid decreased by 25, 51, and 61% compared with the control, respectively. The pH increased to 3.2, 3.81, and 6.65 in the 1, 5, and 25 mg/kg bw DON group, compared with the control (1.9). To examine the mucosal injuries, the stomach tissues were made into hematoxylin and eosin slides. Histopathology observations suggest that no mucosal lesions were observed until DON exposure at 25 mg/kg bw. Additionally, the gastrin secretion in the fluids and mRNA expression in tissues were determined by the radioimmunoassay and real-time PCR assay, respectively. The results indicated that both significantly decreased in DON-exposed rats compared with the control. Taken together, DON exposure reduced gastric secretion in rats. Low gastrin secretion and mRNA expression play a major role, unless mucosal lesions by high DON exposure are present.

Immunohistochemical Localization of Gastrin Cells (G-Cells) in the Alimentary Canal of a Skipper Frog, Euphlyctis cyanophlyctis, Schiedner, (Anura; Ranidae)

The present investigation deals with the immunohistochemical localization of gastrin secreting cells in different parts of the alimentary canal of an insectivorous skipper frog, Euphlyctis cyanophlyctis (Schiedner). The gastrin immunoreactive (G IR) cells have been observed in stomach and in duodenal regions of the gut only. Three different morphological types of G IR cells have been recorded. The first type was with long protoplasmic extension projecting towards the lumen indicating lumone nature of secretion. The second type were rounded or oval in shape present towards basal region adjacent to gastric gland suggesting a non-secretory or parahormone or notch signal property of secretory molecule. The third type of cell was with multiple protoplasmic projections related to the secretory behaviour of gastrin cell. In stomach the G IR cells were more in pyloric region and less in fundic region. In stomach, the first type dominates in its number and the two latter types were less. In the duodenal region, the majority of G IR cells were of second type with scanty first type. It is concluded that the three different morphotypes of G IR cells are in fact different secretory stages of gastrin cells (G cells). The existence of different morphotypes of G cells is also linked with their strategic location and requirement to act as either hormone or parahormone or neurohormone or lumone.

Zollinger–Ellison Syndrome

BackgroundZollinger–Ellison (ZE) syndrome is characterized by gastric acid hypersecretion and ulcer disease from autologous gastrin secretion by a gastrinoma. Patient and methodsA 43 year old man underwent upper endoscopy for a 6 week history of recurrent nausea, vomiting, heartburn, weight loss, and watery diarrhea. ResultsEndoscopic findings included severe reflux esophagitis with multiple linear esophageal ulcerations, thickened gastric folds with mosaic pattern mucosa, distinctive gastric corpus and antrum junction, numerous antral erosions with traces of coffee ground substance, bulbar erosions and ulcerations, and post-bulbar erosions and ulcerations. Based on these symptoms and endoscopic findings, a gastrinoma work-up was instituted and the diagnosis was confirmed. ConclusionsEndoscopists need to be aware of the classical symptoms and clinical findings associated with ZE syndrome in order to appropriately diagnose and manage affected patients.

Motilin and Gastrin Secretion and Lipid Profile in Preterm Neonates Following Prebiotics Supplementation

Gut hormones play an important role in the adaptation of the immature neonatal gut, and their secretion may be modulated by prebiotics. Furthermore, prebiotics are well known for their hypolipidemic potentials. We tested the hypothesis that prebiotics could alter motilin and gastrin secretion and reduce lipids in healthy preterms. A total of 167 newborns were randomized to either a prebiotics enriched formula containing dietary oligosaccharides (short-chain galacto-oligo-saccharides/long-chain fructo-oligo-saccharides [scGOS/lcFOS]), at a concentration of 0.8 g/100 ml, or a common preterm formula. Day 1 and 16 basal motilin, gastrin concentrations, and lipids were evaluated together with growth parameters, gastric residue, bowel habits, and feeding tolerance. Adverse events including necrotizing enterocolitis (NEC) and septicemia were also recorded. Mean motilin increase and day 16 mean values were greater for the intervention, compared with the control group (P = .001, P = .005, respectively), while gastrin remained high in both groups. Mean cholesterol and low density lipoprotein (LDL) increase were significantly greater in the control, compared with the intervention (P = .037, and P = .001) group. Day 16 LDL levels were significantly higher in the control group. Mean weight was increased in the control group, while gastric residue was less and stool frequency was increased in the intervention group. NEC and septicemia were not statistically different between groups. A prebiotics enriched formula resulted in significant surge of motilin relating to reduced gastric residue, compared with a common preterm formula. Mean cholesterol change was lower, while LDL was not increased in the prebiotics group, compared with the control group.

The effect of glucagon-like peptide-1 on the secretion of cholecystokinin and gastrin in patients with type-1 diabetes and healthy subjects

Objective: Ingestion of a meal is known to trigger a rise in plasma concentrations of glucagon-like peptide-1 (GLP-1), cholecystokinin (CCK) and gastrin. These hormones are known to have important roles in the regulation of gastrointestinal motility and secretion, appetite and food intake. There is limited information relating to any possible interaction between these three hormones. However, it has been suggested that the combination of GLP-1, CCK and gastrin provides beneficial effects in the treatment of diabetes.

Primary Lymph Node Gastrinoma Resulting in Zollinger-Ellison Syndrome

Purpose: A 63-year-old man presented with 4 months of non-bloody diarrhea, with 30 bowel movements daily; diarrhea persisted at night while fasting. There was an associated 70-pound unintentional weight loss, along with rare heartburn partially relieved with antacids. Computed tomography of the abdomen revealed a 4.7-cm enhancing mass in the midline adjacent to or arising from the uncinate process of the pancreas. Serum gastrin, obtained off of a proton-pump inhibitor (PPI) was elevated to 1270 pg/mL. Esophagogastroduodenoscopy revealed severe erosive esophagitis and innumerable duodenal bulb and post-bulbar ulcers. Gastric rugae were thickened with large amounts of reaccumulating secretions that had a bedside pH of 3.5. Based on these findings, Zollinger-Ellison syndrome (ZES) was diagnosed. Octreotide scan demonstrated uptake in the lesion seen on CT with no liver lesions. The patient was started on IV PPI with resolution of abdominal pain and diarrhea. Exploratory laparotomy demonstrated, within the gastrinoma triangle, a well-circumscribed 4 x 5-cm mass, which was mobile and not fixed to the pancreas or other adjacent structures. Pancreas and duodenum were palpated extensively with no evidence of occult lesions; the mass was then excised. Pathology with staining determined the tumor to be a primary lymph node (LN) gastrinoma. Post-operatively, diarrhea resolved and there was gradual weight gain. Gastrin level normalized and PPI was eventually discontinued. ZES is caused by the autonomous secretion of gastrin by gastrinomas. Ninety percent of gastrinomas occur in an anatomic area called the gastrinoma triangle, classically in the pancreas or duodenal wall. Surgical resection can result in cure and should be pursued in patients with resectable disease. Not all gastrinomas in LN result from metastatic spread from pancreatic primaries, but rather may be primary LN tumors as shown in our case. This is supported by the absence of gastrinoma in other locations and normalization of gastrin levels postoperatively. Primary LN gastrinomas do not have any distinguishing characteristics compared to other types of gastrinomas. All patients with ZES proceeding to surgery should have detailed exploration to rule out pancreatic or duodenal tumors, as well as routine excision of LNs within the gastrinoma triangle. The existence of primary LN gastrinomas is controversial, although one study suggests they may occur in 10% of ZES cases. They do not occur in MEN 1. They are unique in that they have been cured by lymph node excision alone. This case demonstrates that gastrinomas may develop primarily in LNs rather than the more commonly suspected solid organs.

Analysis of possible causes of activation of gastric and the pancreatic excretory and incretory function after completion of space flight at the international space station

A comparative analysis of the excretory and incretory activity of the stomach and pancreas in astronauts soon after completion of space flights of various durations was performed. An increase in the fasting activity of gastric and pancreatic enzymes and hormones (insulin and C-peptide) in blood, reflecting the increased excretory and incretory activity of organs of the gastroduodenal region developing in microgravity, was demonstrated. The absence of subjects infected with Helicobacter pylori in the space flight crew excluded the involvement of this microorganism in the mechanism underlying the increase in the gastric secretory activity. The absence of correlation between the increase in the secretory activity of organs of the gastroduodenal region and the duration of the space flight allowed us to rule out the hypokinetic mechanism, which is associated with the duration of exposure to microgravity. It was concluded that the main mechanism underlying the changes in the functional state of the digestive system in space flight may be determined by the rearrangement of the venous hemodynamics of organs of the abdominal cavity, unrelated to the duration of exposure to microgravity. It was shown that, after completion of space flights and in ground-based experiments simulating the hemodynamic rearrangement occurring in microgravity, the increase in the basal excretory activity of gastroduodenal organs was not caused by gastrin secretion and occurred simultaneously with an increase in the secretion of insulin, which is considered as a putative hormonal component of the hemodynamic mechanism.

28 Cell-Specific Deletion of Primary Cilia on G-Cells Alters Food Induced Gastrin Secretion

28 Cell-Specific Deletion of Primary Cilia on G-Cells Alters Food Induced Gastrin Secretion

A thymic carcinoid tumour causing Zollinger-Ellison and Cushing’s syndromes due to ectopic ACTH and gastrin secretion

Cushings’s syndrome due to ectopic adrenocorticotrophin (ACTH) secretion was first described nearly a century ago by Hurst Brown. Bronchial carcinomas, usually bronchial carcinoids, were the first to be described and continue to be the leading cause of the ectopic ACTH syndrome; however, thymic carcinoids account for approximately 10% of cases. The Zollinger Ellison syndrome, excessive gastrin secretion from a neuroendcorine tumour, has been described as exclusively due to neuroendocrine tumours of entero-pancreatic origin, while secretion of gastrin from a thymic carcinoid tumour has not been reported to our knowledge. We report a unique case of a 34-year-old woman with ACTH-dependent Cushing’s syndrome and Zollinger-Ellison syndrome due to a thymic carcinoid tumour. caSe report

Primary cilia regulate gastrin secretion in GLUTag cells

Primary cilia (PC) are sensory organelles that we recently reported are expressed on endocrine cells of the stomach. Deletion of PC on the gastric mucosa resulted in higher plasma gastrin (Gast) levels. Therefore we hypothesized that PC on endocrine cells modulate Gast secretion. Recently we discovered that GLUTag cells present PC, in addition to expressing and releasing Gast. To define the extracellular signals regulating PC, GLUTag cells were treated with 20 mM glucose, 2% peptone, 5μM forskolin, 100 nM octreotide and 50 μM omeprazole. After 2 h tratment, PC were stained with anti‐acetylated tubulin and counted. Secreted Gast and GLP‐1 were measured and normalized to cell content. We found that glucose induced GLP‐1 but not Gast secretion and had no effect on PC. Peptone reduced PC numbers and induced Gast but not GLP‐1. Forskolin induced secretion of both hormones without affecting PC presentation. Octreotide reduced the secretion of both hormones without changing PC. However, omeprazole reduced PC numbers and increased Gast but not GLP‐1 secretion. Our data suggest that PC presentation is regulated by extracellular signals. Reduction of PC stimulated Gast secretion. PC were not associated with GLP‐1 secretion. Therefore, we concluded that GLUTag cells are a good model to study Gast release, and that PC regulate Gast but not GLP‐1 secretion. Research support: P01‐DK62041 and 5P30DK034933

Lack of cholinergic innervation in gastric mucosa does not affect gastrin secretion or basal acid output in neurturin receptor GFRα2 deficient mice

Efferent signals from the vagus nerve are thought to mediate both basal and meal-induced gastric acid secretion, and provide trophic support of the mucosa. However, the underlying mechanisms are incompletely understood. Neurturin, signalling via glial cell line-derived neurotrophic factor (GDNF)-family receptor α2 (GFRα2), is essential for parasympathetic innervation of many target tissues but its role in gastric innervation is unknown. Here we show that most nerve fibres in wild-type mouse gastric mucosa, including all positive for gastrin-releasing peptide, are cholinergic. GFRα2-deficient (KO) mice lacked virtually all cholinergic nerve fibres and associated glial cells in the gastric (oxyntic and pyloric) mucosa but not in the smooth muscle, consistent with the selective expression of neurturin mRNA in the gastric mucosa. 2-Deoxyglucose and hexamethonium failed to affect acid secretion in the GFRα2-KO mice indicating the lack of functional innervation in gastric mucosa. Interestingly, basal and maximal histamine-induced acid secretion did not differ between wild-type and GFRα2-KO mice. Moreover, circulating gastrin levels in both fasted and fed animals, thickness of gastric mucosa, and density of parietal and different endocrine cells were similar. Carbachol-stimulated acid secretion was higher in GFRα2-KO mice, while atropine reduced basal secretion similarly in both genotypes. We conclude that cholinergic innervation of gastric mucosa depends on neurturin-GFRα2 signalling but is dispensable for gastrin secretion and for basal and maximal acid output. Basal acid secretion in the KO mice appears to be, at least partly, facilitated by constitutive activity of muscarinic receptors.