Increased Gastrin Secretion Research Articles

REBOUND PHENOMENON OF PROTON PUMP INHIBITOR THERAPY

Proton pump inhibitors (PPIs) are the most potent drugs for suppressing gastric acid secretion. They are used in the treatment of acid-peptic disorders, including peptic ulcer disease, gastroesophageal reflux disease, Zollinger Ellison syndrome, in the eradication of Helicobacter pylori infection and ulcer prophylaxis. In the pharmacotherapy of these disorders, they have significantly suppressed the use of H2 blockers, like other, older groups of antisecretory drugs. Long-term PPI therapy leads to moderate hypergastrinemia (increased gastrin secretion) in 20-25% of patients. This hypergastrinemia results in rebound acid hypersecretion (RAHS) in 30-40% patients, who abruptly discontinue PPI. Most patients who abruptly discontinue PPI have symptoms of dyspepsia and gastroesophageal reflux, most commonly heartburn and a burning sensation in the esophagus. Therefore, care should be taken to properly discontinue PPI and reduce the dose of the drug before complete discontinuation. A less effective acid blocker (H2 blocker) can be switched, since H2 receptor blockers cause less pronounced hypergastrinemia and hyperplasia of enterochromaffin-like cells (ECL cells) compared to PPI.

Interleukin-1β Suppresses Gastrin via Primary Cilia and Induces Antral Hyperplasia.

Background & AimsHelicobacter pylori infection in humans typically begins with colonization of the gastric antrum. The initial Th1 response occasionally coincides with an increase in gastrin secretion. Subsequently, the gastritis segues to chronic atrophic gastritis, metaplasia, dysplasia and distal gastric cancer. Despite these well characterized clinical events, the link between inflammatory cytokines and non-cardia gastric cancer remains difficult to study in mouse models. Prior studies have demonstrated that overexpression of the Hedgehog (HH) effector GLI2 induces loss of gastrin (atrophy) and antral hyperplasia. To determine the link between specific cytokines, HH signaling and pre-neoplastic changes in the gastric antrum.MethodsMouse lines were created to conditionally direct IL1β or IFN-γ to the antrum using the Gastrin-CreERT2 and Tet activator. Primary cilia, which transduces HH signaling, on G cells were disrupted by deleting the ciliary motor protein KIF3a. Phenotypic changes were assessed by histology and western blots. A subclone of GLUTag enteroendocrine cells selected for gastrin expression and the presence of primary cilia was treated with recombinant SHH, IL1β or IFN-γ with or without kif3a siRNA.ResultsIFN-γ increased gastrin and induced antral hyperplasia. However, antral expression of IL1β suppressed tissue and serum gastrin, while also inducing antral hyperplasia. IFN-γ treatment of GLUTAg cells suppressed GLI2 and induced gastrin, without affecting cilia length. By contrast, IL1β treatment doubled primary cilia length, induced GLI2 and suppressed gastrin gene expression. Knocking down kif3a in GLUTAg cells mitigated SHH or IL1β suppression of gastrin.ConclusionsOverexpression of IL1β in the antrum was sufficient to induce antral hyperplasia coincident with suppression of gastrin via primary cilia. ORCID: #0000-0002-6559-8184

Autologous reconstructive surgery and intestinal rehabilitation in the management of short bowel syndrome

Based on the latest definition, short bowel syndrome is defined as intestinal failure due to the loss of significant small bowel length or function, when the homeostasis and growth can only be maintained with intravenous supplementation of fluid, electrolytes and macronutrients. The natural adaptation of the short bowel can only compensate for the loss up to a certain level. According to this, we differentiate (1) acute, (2) prolonged and (3) chronic types of intestinal failure/short bowel syndrome. The most common causes are necrotising enterocolits, intestinal malrotation and volvulus, gastroschisis and ileal atresia. The management of type 3 short bowel syndrome has evolved significantly during the last decades, due to the multidisciplinary approach, hence the survival and quality of life of the patients have improved and transplantation is rarely necessary. Our aim was to review the most important considerations of intestinal rehabilitation, like management of increased gastrin secretion, high output stoma, decreased transit time, central venous lines, enteral and parenteral nutrition and the enhancement of the natural adaptation. We reviewed the former and the latest options of the autologous intestinal reconstructive surgery (AIRS) like the reversed segment, small bowel interposition, ileocaecal valve replacement, bowel lengthening and tailoring (LILT, STEP and SILT), controlled bowel expansion and the latest results with distraction enterogenesis and tissue engineering. Orv Hetil. 2020; 161(7): 243-251.

Stomach gastrin is regulated by sodium via PPAR-α and dopamine D1 receptor

Gastrin, secreted by stomach G cells in response to ingested sodium, stimulates the renal cholecystokinin B receptor (CCKBR) to increase renal sodium excretion. It is not known how dietary sodium, independent of food, can increase gastrin secretion in human G cells. However, fenofibrate (FFB), a peroxisome proliferator-activated receptor-α (PPAR-α) agonist, increases gastrin secretion in rodents and several human gastrin-secreting cells, via a gastrin transcriptional promoter. We tested the following hypotheses: (1.) the sodium sensor in G cells plays a critical role in the sodium-mediated increase in gastrin expression/secretion, and (2.) dopamine, via the D1R and PPAR-α, is involved. Intact human stomach antrum and G cells were compared with human gastrin-secreting gastric and ovarian adenocarcinoma cells. When extra- or intracellular sodium was increased in human antrum, human G cells, and adenocarcinoma cells, gastrin mRNA and protein expression/secretion were increased. In human G cells, the PPAR-α agonist FFB increased gastrin protein expression that was blocked by GW6471, a PPAR-α antagonist, and LE300, a D1-like receptor antagonist. LE300 prevented the ability of FFB to increase gastrin protein expression in human G cells via the D1R, because the D5R, the other D1-like receptor, is not expressed in human G cells. Human G cells also express tyrosine hydroxylase and DOPA decarboxylase, enzymes needed to synthesize dopamine. G cells in the stomach may be the sodium sensor that stimulates gastrin secretion, which enables the kidney to eliminate acutely an oral sodium load. Dopamine, via the D1R, by interacting with PPAR-α, is involved in this process.

Helicobacter pylori-Induced Changes in Gastric Acid Secretion and Upper Gastrointestinal Disease.

Appropriate management of Helicobacter pylori infection of the human stomach is evolving and remains a significant clinical challenge. Acute infection results in hypochlorhydria, whereas chronic infection results in either hypo- or hyperchlorhydria, depending upon the anatomic site of infection. Acute hypochlorhydria facilitates survival of the bacterium and its infection of the stomach. Interestingly, most patients chronically infected with H. pylori manifest a pangastritis with reduced acid secretion due to bacterial virulence factors, inflammatory cytokines, and various degrees of gastric atrophy. While these patients are predisposed to develop gastric adenocarcinoma (~1%), there is increasing evidence from population studies that they are also protected from gastroesophageal reflux disease (GERD), Barrett's esophagus (BE), and esophageal adenocarcinoma (EAC). Eradication of H. pylori, in these patients, may provoke GERD in predisposed individuals and may be a contributory factor for the rising incidence of refractory GERD, BE, and EAC observed in Westernized societies. Only ~10% of chronically infected patients, mainly the young, manifest an antral predominant gastritis with increased acid secretion due to a decrease in somatostatin and increase in gastrin secretion; these patients are predisposed to develop peptic ulcer disease. H. pylori-induced changes in acid secretion, in particular hypochlorhydria, may allow ingested microorganisms to survive transit through the stomach and colonize the distal intestine and colon. Such perturbation of gut microbiota, i.e. dysbiosis, may influence human health and disease.

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.

Helicobacter pylori and gut hormones.

Helicobacter pylori infection has been found to decrease the expression of antral somatostatin and to increase the release of the acid-stimulating hormone gastrin. The reversal of these changes in gut hormones by the eradication of H. pylori, and in-vivo and in-vitro studies in animals either infected with H. pylori or exposed to H. pylori-related materials may support the somatostatin-gastrin link theory in the pathophysiology of H. pylori infection. The following mechanisms have been proposed to explain the H. pylori infection-associated changes in gut hormones; (1) ammonia produced by H. pylori and monochloramine, (2) effect on somatostatin receptor subtype-2, (3) action of lipopolysaccharide from H. pylori on somatostatin receptor, (4) inflammatory cells and mediators, and (5) bacterial strain diversity. H. pylori infection can alter gastric acid secretion in both directions. The elevated acid secretion in patients with duodenal ulcer is decreased by H. pylori eradication, and is accompanied by the normalization of gut hormones in patients whose H. pylori-induced gastritis is limited to the antrum with hyperacidity. Corpus gastritis and the subsequent development of mucosal atrophy induced by H. pylori result in decreased acid secretion, although the mechanism underlying H. pylori-induced atrophy in some subjects remains unclear. Hypoacidity enhances corpus atrophy and increases gastrin secretion, mediated via a physiological suppression of somatostatin release, features that are also observed in H. pylori infection. Therefore, the capacity of acid secretion and distribution of gastritis or atrophy should be taken into consideration when we discuss the affect of H. pylori on gut hormones.

Effect of intragastric ammonia on gastrin-, somatostatin- and somatostatin receptor subtype 2 positive-cells in rat antral mucosa

Somatostatin suppresses gastrin and somatostatin secretion via somatostatin receptors (SSTRs). Ammonia produced by Helicobacter pylori has been reported to modify gastric gastrin and somatostatin levels. We investigated the distribution of SSTR-subtype 2 (SSTR-2) in relation to gastrin- and somatostatin-containing cells and the effect of ammonia solution (0.01%–0.1%) administered orally for 2 to 4 weeks on these cells in rat antral mucosa by immunohistochemistry. The majority of SSTR-2 peptide [31–41]-positive cells were located in the basal third of the glands. Double staining experiments revealed that SSTR-2 peptide [31–41]-positive cells are co-localized in 85.0 ± 2.2% of the gastrin-containing cells and in 34.4 ± 4.8% of the somatostatin-containing cells. Ammonia solution significantly decreased the number of somatostatin-containing cells and increased the proportion of SSTR-2 peptide [31–41]-labeling in the somatostatin-containing cells in a duration-dependent manner. Maximum changes were observed in rats treated with ammonia solution at the lowest level of 0.01% accompanied by an increase in serum gastrin levels in the portal vein. Sodium hydroxide at the similar pH to 0.01% ammonia solution had no effect. These findings suggest that SSTR-2 are localized in antral endocrine cells and that ammonia solution mainly decreases somatostatin-containing cells without SSTR-2 expression, resulting in an increase in gastrin secretion into the portal vein.

Concurrent elevation of fundic somatostatin prevents gastrin stimulation by GRP.

Gastrin-releasing peptide (GRP) can stimulate both gastrin and somatostatin (SOM) secretion, but, as gastrin increases SOM and SOM in turn inhibits gastrin, the overall endpoint in terms of gastrin output is variable. To examine the mechanisms involved, we compared the effects of GRP on gastrin secretion in normal sheep and sheep chronically immunized against SOM. In the normal animal, GRP had no effect on either plasma gastrin or SOM. However, in sheep immunized against SOM, GRP stimulated gastrin secretion, suggesting that the concurrent stimulation of SOM prevents the increase in gastrin secretion. To determine the local source of SOM, GRP was then infused into nonimmunized sheep with cannulas draining blood from the fundus and antrum. GRP stimulated fundic SOM output but inhibited antral SOM and gastrin secretion, demonstrating that the fundus was the source of the SOM. Because cholinergic interactions have a major influence on the effects of GRP, a cholinergic stimulus was administered, and we found that the responses were different: SOM output was inhibited in both the antrum and fundus, and antral gastrin secretion was increased. The present study demonstrates two further instances of the differential regulation of SOM from the antrum and fundus. GRP fails to stimulate gastrin because of an increase in fundic SOM, whereas gastrin levels increase following a cholinergic stimulus because of inhibition of both antral and fundic SOM secretion.

Helicobacter pylori-infected human antral primary cell cultures: effect on gastrin cell function.

Although Helicobacter pylori infection increases gastrin secretion, it is unknown whether this is a direct effect or requires activation of the immune system. We developed an H. pylori-infected human primary antral epithelial cell culture model to address this question. This culture protocol favors growth of H. pylori, and infected cultures could be maintained for up to 48 h. These cultures were enriched for gastrin (10-40%), somatostatin (2-5%), and gastric mucin (60-80%) cells but did not contain immunocytes. Bacterial attachment occurred in a random manner within 2 h of infection, although bacterial density was lower than in sections from infected patients. After 24 or 48 h, the bacterial microcolonies were similar in size to those seen in vivo, and at 24 h ultrastructural studies demonstrated well-developed pedestal formation underlying the bacteria. Coculture with H. pylori increased basal but not stimulated gastrin secretion at all time points >2 h. In conclusion, a newly developed cell culture model has been used to characterize the interactions between H. pylori and normal human antral epithelial cells.

Role of acetylcholine and gastrin-releasing peptide (GRP) in gastrin secretion.

Using an isolated rat stomach infusion model, we investigated the role of gastrin-releasing peptide (GRP) and acetylcholine in the secretion of gastrin (which plays a major role in gastric acid secretion), and the relationship between gastrin secretion and stomach pH. Bombesin, which has a structure analogous to that of GRP, was used in the experiment. We also investigated whether acetylcholine has muscarine-like or nicotine-like action. Our findings pointed to the presence of an alternative, GRP-mediated, route for stimulating gastric secretion from G cells, other than the acetylcholine-mediated route. We injected bombesin to confirm the presence of such a GRP-mediated route; significantly increased gastrin secretion was observed, even under acidic conditions, in the gastric lumen, which has been considered to show almost no gastric secretion. This secretion was not inhibited by atropine. The results suggested that there are two routes for inducing gastrin secretion from G cells: an acetylcholine-mediated route and a GRP-mediated route (intramural peptide neurons). As GRP induced gastrin secretion, regardless of stomach pH, GRP was considered to be more closely related to gastrin secretion. The results also suggested that a muscarine-like action, particularly in the M3 receptor-mediated route, plays a significant role in acetylcholine-mediated gastrin secretion and that nicotine-like action is not involved in gastrin secretion.

Mediators of antigen-induced gastrin release: role of antigen-antibody complexes and the complement system.

That orally administered antigen was shown to induce gastrin release in immunized animals was a new aspect of gastrointestinal physiology. The mediators responsible for this immunological effect are still unclear. In an attempt to discover more about the mechanisms regarding antigen-induced gastrin release, we developed an in vitro system where fragments of rat antral mucosa were challenged. This makes it possible to determine the role of antigen-antibody complexes and the complement system in the mechanism of antigen-induced gastrin release. Wistar rats were immunized in vivo with NIP-OVA and mucosal fragments were challenge, in vitro with NIP-HGG. Gastrin was determined after a preincubation and a challenged incubation period without supernatants. After antigenic challenge, supernatants were used for in vitro challenge in order to rule out the presence of a soluble mediator and activation of complement. In a second group of experiments Wistar rats were used to study in vitro the release of specific antibodies after antigenic challenge. With this experimental design we were able to show increased gastrin secretion after antigenic challenge in vitro in the presence of intact tissue. It is shown that the increased gastrin release is most probably mediated by activation of the complement system in the presence of antigen-antibody complexes. These are built up by specific anti-NIP antibodies and NIP-HGG used for the challenge. The complement system might be the final pathway of the observed increased gastrin release.

Cimetidine and omeprazole accelerate gastric ulcer healing by an increase in gastrin secretion.

Daily oral administration of cimetidine or omeprazole markedly accelerated the healing of acetic acid-induced gastric ulcers in rats with a limited food intake time. The increased gastric acid secretion induced by daily treatment with histamine affected neither the spontaneous healing of the ulcers nor the healing-promoting actions of both agents. Pretreatment of rats with ulcers with 6-hydroxydopamine significantly inhibited the increase in the antrum gastrin cells, serum gastrin levels and corpus mucosal thickness elicited by repeated administration of cimetidine or omeprazole. Pretreatment with 6-hydroxydopamine did not affect the inhibitory actions of cimetidine and omeprazole on acid secretion, but completely abolished the ulcer healing-promoting actions of both drugs. Daily intraperitoneal administration of pentagastrin accelerated ulcer healing. These results suggest that cimetidine and omeprazole mainly accelerate the healing of gastric ulcers by the trophic action of gastrin via the increase in gastrin secretion, while the inhibition of acid secretion may play a minor role in ulcer healing.

Gastric inhibitory polypeptide and glucagon-like peptide-1(7–36) amide exert similar effects on somatostatin secretion but opposite effects on gastrin secretion from the rat stomach

Previous studies on the isolated perfused stomach have shown that gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1(7-36) amide (GLP-1(7-36) amide) stimulate release of somatostatin (somatostatin-like immunoreactivity, SLI). GIP produced a paradoxical increase in gastrin secretion, whereas GLP-1(7-36) was inhibitory. In the current study, the actions of synthetic (sp) and native (np) porcine and synthetic human (sh) GIP, GLP-1(7-36), and GLP-1(7-37) on SLI and gastrin secretion were compared using a gradient perfusion of peptide. All peptides increased SLI secretion at a threshold concentration of approximately 50 pmol/L (p < 0.05). The initial rate of increase in response to spGIP (119 +/- 39 pg/min) was greater than with other forms of GIP or GLP-1. Maximal increases obtained with the two porcine peptides did not differ. Gastrin secretion was increased by concentrations of spGIP and npGIP similar to those increasing SLI secretion, but the maximal response to shGIP was lower. In contrast to GIP-induced increases, both GLP-1(7-36) and GLP-1(7-37) suppressed gastrin secretion. It is concluded that human and porcine GIP, GLP-1(7-36), and GLP-1(7-37) all stimulate SLI secretion but with different maximal effects, and GIP stimulates gastrin secretion whereas both forms of GLP-1 inhibit gastrin secretion.

Gastrin and somatostatin in Helicobacter pylori infected antral mucosa.

Helicobacter pylori infection is associated with increased meal stimulated gastrin secretion, but the reason for this is unknown. Sequence specific radioimmunoassays were used to measure the concentration of alpha-amidated gastrin, the total progastrin product, and somatostatin in biopsy specimens of human antral mucosa. The antral concentrations of alpha-amidated gastrin and of total progastrin products were significantly higher in H pylori infected patients than in those not infected by this organism. In contrast, the antral somatostatin concentration was significantly decreased in infected patients. Progastrin processing, determined by gel chromatography, seemed unaffected by H pylori infection. The results suggest that the finding of increased gastrin secretion from the antral G cells in H pylori infected patients may be a result of reduced inhibition of G-cell secretion by somatostatin.

Antral G-cell and D-cell numbers in Helicobacter pylori infection: Effect of H. pylori eradication

Background: It has recently been recognized that Helicobacter pylori infection is associated with abnormalities in the regulation of gastrin secretion. We investigated whether there was a relationship between H. pylori infection and G-cell and D-cell numbers. Methods: The numbers of antral G cells and D cells were compared between 20 patients with duodenal ulcer and 24 volunteers, 12 with and 12 without H. pylori infection. The effect of eradication of H. pylori infection on G-cell number was also evaluated. Antral mucosal biopsy specimens were examined using immunohistochemical techniques specific for the presence of gastrin and somatostatin. Results: The number of G cells was significantly (P < 0.02) less in patients with duodenal ulcer than in either infected or uninfected controls (3.7 0.3 vs. 6.2 ± 0.6 and 5.3 ± 0.5 G cells per gland for infected and uninfected controls, respectively). The ratio of G-cells to D-cells was similar in duodenal ulcer patients (2.2) and uninfected controls (2.0). It was found that, although eradication of the H. pylori infection results in a dramatic reduction in stimulated gastrin secretion, it is not associated with a change in the numbers of antral G cells or D cells in patients with duodenal ulcer. Conclusions: It is concluded that H. pylori infection-associated increase in gastrin secretion appear to be related to local factors regulating G-cell function.

Somatostatin restraint of gastrin secretion in pigs revealed by monoclonal antibody immunoneutralization.

We studied the functional coupling between antral somatostatin and gastrin cells in isolated perfused porcine antrum using immunoneutralization with monoclonal antibodies against somatostatin. Their binding affinity was 10(11) l/mol, and the final binding capacity was 11.7 nmol/ml. Antibody infusion within 1 min increased gastrin secretion, reaching a rate of 349 +/- 64% (means +/- SE, n = 7) of basal secretion (59 +/- 5 pmol/l) after 5 min. The effect of somatostatin at 10(-9) mol/l, which inhibited gastrin secretion from 58 +/- 11 to 14 +/- 3 pmol/min (n = 4), was abolished by antibody infusion. Electrical stimulation of the vagus nerves (n = 7) performed during antibody infusion increased gastrin secretion from 224 +/- 61 to 328 +/- 55 pmol/min, not significantly different from the increase in control experiments from 43 +/- 9 to 118 +/- 20 pmol/min, indicating that the vagal stimulation of gastrin secretion does not depend on mechanisms involving somatostatin. We conclude that paracrine antral somatostatin secretion is one of the most important factors regulating basal gastrin secretion in pigs.

Meal-stimulated exocrine pancreatic secretion and release of GI peptides in normal and nicotine-treated rats

In rats, treated chronically with saline and nicotine, we studied the postprandial release of gastrin and cholecystokinin by specific radioimmunoassays and simultaneously measured secretory outputs of the exocrine pancreas. Rats were prepared surgically with gastric and pancreatic fistulas. Meal-stimulated release of peptides and exocrine secretory outputs were measured 24 h postoperatively in conscious rats. Infusion of food via intragastric cannula significantly stimulated plasma gastrin levels in both control and nicotine treated rats. Postprandial gastrin levels in nicotine treated rats were significantly higher compared to gastrin levels obtained after food in untreated control rats. Plasma CCK levels were increased in both groups after food. These levels remained significantly elevated from the basal values only for a transient period following infusion of the liquid meal. There were no differences in postprandial plasma CCK levels between the two groups. Outputs of exocrine pancreatic volume, protein and trypsin increased significantly after food in both control and nicotine treated groups of rats. The differences in outputs of volume and protein between the two groups of rats were not significant; however, the trypsin outputs in the nicotine rats were decreased significantly when compared to control rats. The data indicate that in rats, administration of food stimulated the release of immunoreactive gastrin and CCK with concomitant increase in exocrine pancreatic secretions of volume, protein and trypsin. Chronic nicotine treatment and its effect on food, however, appeared to have induced hyperfunction of G-cells that resulted in increased gastrin secretion and a decrease in trypsin secretion by exocrine pancreas. These data may have important implications in the etiology of the development of exocrine pancreatic dysfunction in chronic smokers.

Effect of a purified somatostatin monoclonal antibody and its Fab fragments on gastrin release

The effect of a purified somatostatin monoclonal antibody, SOMA 10, and its Fab fragments on gastrin release have been examined in the isolated perfused rat stomach. SOMA 10 was purified from ascites fluid by ammonium sulfate precipitation followed by hydroxylapatite (HAP) chromatography. This gave a preparation of greater than 90% purity, as assessed by fast affinity and size exclusion high-performance liquid chromatography (HPLC). HAP-purified SOMA 10 had a binding capacity of 760 mmol somatostatin/mol antibody, a dissociation constant of 2.2 nM, and recognized amino acid residues 5-12 of the somatostatin molecule. Fab fragments of SOMA 10 were prepared and purified by protein A affinity chromatography, and the purity assessed by HPLC and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Single passage perfusion of SOMA 10 (100 micrograms/ml) into the gastric vasculature caused a paradoxical decrease in basal gastrin release. However, recirculation of the antibody (20 micrograms/ml) caused an increase in cumulated gastrin release. Perfusion of Fab fragments of SOMA 10 (66 micrograms/ml) also increased gastrin secretion. These results support the suggestion that somatostatin exerts a tonic restraint on gastrin release and that penetration of the antibody to the site of somatostatin release is necessary for it to have an effect.

DO ALCOHOLIC BEVERAGES HAVE AN ADDITIONAL EFFECT ON THE POSTPRANDIAL GASTRIN RESPONSE IN HUMANS?

The hormone gastrin plays an important role in the regulation of acid secretion in the stomach which, in turn, stimulates the digestion of food. Previous studies reported that administration of beer and wine but not ethanol and spirits increases gastrin secretion in fasting volunteers. It is not known whether alcoholic beverages combined with a normal meal have an additional effect on the postprandial gastrin response. We therefore measured the gastrin response in eight volunteers who received either alcoholic beverages (40 g alcohol) in the form of beer, red wine or spirits, or mineral water as control in combination with a dinner. Two glasses were drunk before the meal, two glasses during the meal. Plasma gastrin concentrations were twofold increased at one hour after the dinner as compared to predinner values. However, no additional effect of beer, wine or spirits on this postprandial response was seen. The present study does not support the hypothesis that the consumption of beer or wine during a meal has a positive effect on the release of gastrin and therefore most probably does not contribute to an improved digestion of food by stimulation of acid secretion.