Maximal Gastric Acid Output Research Articles

Activation of the calcium sensing receptor stimulates gastrin and gastric acid secretion in healthy participants

In 17 adults on a fixed metabolic diet, an 11-day course of cinacalcet increased serum gastrin and basal gastric acid output, but not maximal gastric acid output, compared with a placebo. These findings indicate that the calcium sensor receptor plays a role in the regulation of gastric acid. Gastric acid secretion is a complex process regulated by neuronal and hormonal pathways. Ex vivo studies in human gastric tissues indicate that the calcium sensing receptor (CaR), expressed on the surface of G and parietal cells, may be involved in this regulation. We sought to determine whether cinacalcet, a CaR allosteric agonist, increases serum gastrin and gastric acid secretion. Seventeen healthy adults with normal gastric acid output were placed on an 18-day metabolic diet. On day 8 (baseline), participants were given cinacalcet (15 then 30 mg/day) or placebo for 11 days. Changes in gastric acid output, serum gastrin, and other measures were compared in the two groups. Changes in serum gastrin and basal acid output (adjusted for baseline body weight) were significantly more positive in the cinacalcet group compared with placebo (P = 0.004 and P = 0.039 respectively). Change in maximal acid output was similar in the two groups (P = 0.995). As expected, cinacalcet produced significant decreases in serum PTH (P < 0.001) and ionized calcium levels (P = 0.032), and increases in serum phosphorus levels (P = 0.001) and urinary calcium (P = 0.023). This study provides in vivo evidence that activation of the CaR increases serum gastrin levels and basal gastric acid secretion in healthy adults.

Higher Gastric Mucin Secretion and Lower Gastric Acid Output in First-degree Relatives of Gastric Cancer Patients

Patients infected by Helicobacter pylori who have first-degree relatives with gastric cancer have an 8-fold increased risk of developing gastric cancer themselves. Mucins are high-molecular-weight glycoproteins that play a cardinal role in the protective mechanism of the gastric epithelium. To study gastric acid and mucin secretion in dyspeptic patients with and without a family history of gastric cancer and H. pylori infection. Twenty-six dyspeptic patients underwent esophago-gastro-duodenoscopy, gastric biopsies, and acid and mucin secretory tests. The sample was divided by family history of gastric cancer and H. pylori status. Patients who were infected by H. pylori had a significantly higher degree of inflammation than those who were not. H. pylori-positive patients with a positive family history had a lower basal and maximal gastric acid output than infected patients with no family history and noninfected controls, and a higher basal and maximal mucin output than infected patients with no family history. MUC5AC was the major mucin species expressed in gastric juice. In patients with relatives with gastric cancer, H. pylori infection is associated with a more severe inflammatory reaction consisting of decreased gastric acid secretion and increased mucin secretion.

Serum pepsinogen concentrations as a measure of gastric acid secretion in Helicobacter pylori-negative and -positive Japanese subjects

Although previous studies have indicated that serum pepsinogen I levels, as well as the pepsinogen I/II ratio, were positively correlated with maximal gastric output, the relationship may be different between Helicobacter pylori-negative and -positive subjects. The aim of this study was to investigate the relation between serum pepsinogen concentrations and gastric acid secretion in H. pylori-positive and -negative subjects separately. The presence of H. pylori infection, the serum pepsinogen concentrations, and gastric acid secretion were investigated in 182 subjects without localized lesions in the upper gastrointestinal tract. Serum pepsinogen concentration was measured by radioimmunoassay, and maximal gastric acid output was estimated by an endoscopic gastrin test, as we have previously shown. In H. pylori-positive subjects, serum pepsinogen I levels and the pepsinogen I/II ratio were significantly correlated with gastric acid secretion, although the latter showed a better correlation (r=0.40 and 0.53, respectively). On the other hand, in H. pylori-negative subjects, serum pepsinogen concentrations were well correlated with acid secretion (r=0.57), but there was no relation between the pepsinogen I/II ratio and acid secretion. The correlations between serum pepsinogens and gastric acid secretion differ, depending on the presence or absence of H. pylori infection. With the use of serum pepsinogens as a simple measure of gastric acid secretion, therefore, consideration of H. pylori infection status is needed. Because the determination of the acid secretory level has some clinical implications in both H. pylori-positive and -negative subjects, its estimation by serum pepsinogen concentrations can be of practical use.

Modulating the cytokine response to treat Helicobacter gastritis

The conventional view of gastric acid secretion is that a negative feedback mechanism arises in response to high acidity, such that somatostatin keeps G-cells and parietal cells from producing more gastrin and acid, respectively. When the stomach becomes infected, for example with Helicobacter pylori (H. pylori), the feedback mechanism is impaired. In animal models, our laboratory has demonstrated that other types of bacteria besides H. pylori can cause gastritis. For example, under conditions of low acidity, gastritis is secondary to bacterial overgrowth, not production of excessive acid, thus suggesting a new paradigm for the regulation of gastric acid secretion under inflammatory conditions. Cytokines, released during the gastric inflammatory response, including IFNγ, TNFα and IL-1β stimulate the G-cell to produce gastrin. Gastrin in turn triggers the release of acid, and hypergastrinemia suppresses somatostatin, the inhibitor of acid. The overall response results in maximal gastric acid output that acts as the stomach's most important anti-microbial agent. The increased acid secretion by the stomach in the presence of H. pylori seems to be part of the innate immune response, in that gastrin and somatostatin are reciprocally regulated by Th1 or Th2 cytokines, respectively. In a mouse model, we showed that octreotide, a somatostatin, analog, is an efficacious treatment for Helicobacter gastritis. In humans, octreotide might accelerate recovery from H. pylori infection, reducing the duration of antibiotic therapy.

Susceptibility of dopamine D5 receptor targeted mice to cysteamine

Background. Recently we demonstrated that gastric mucosa of rats can synthesize, store and release dopamine. Out of five different subtypes, mRNA of D5 (=D1b) dopamine receptor is very abundant in the gastric epithelium. D1 receptor selective dopamine agonists have been shown to protect against experimental gastro-duodenal lesions. Aims. To test the hypothesis that protective effects of dopamine involve D5 receptors, mucosal lesions were induced in D5 receptor deficient (KO) and wild-type (WT) mice using cysteamine. Morphology and gastric acid secretion of D5 KO mice were also studied. Methods. Single doses of 600 mg/kg, 300 mg/kg cysteamine or vehicle were administered subcutaneously to fasted animals. After 24 h, number and severity of gastro-duodenal lesions were analyzed. Basal and histamine-induced maximal gastric acid output were measured by a stomach-sac wash-through method. Results. All the KOs in the 600 mg/kg cysteamine group died within 4 h showing symptoms of toxicity while three out of four WTs survived ( P<0.05). Mortality after 300 mg/kg cysteamine was significantly higher in KOs versus the WTs: 6/14 versus 2/11, P<0.05. Gastric lesion-index was also significantly higher in KOs (median, middle quartile): four (3–9) versus 0 (0-0), P<0.05. Duodenal lesions did not develop from this single dose of cysteamine in either genotype. Basal and histamine-induced maximal gastric acid output were comparable in the two genotypes. Conclusions. This study demonstrates that loss of D5 receptor causes mucosal vulnerability and increased toxicity of cysteamine in genetically manipulated mice. Thus, D5 receptor subtype is indeed likely to be involved in protective effects of dopamine in the stomach.

Is Familial Hyperpepsinogenemia Associated with

Pepsinogen 1 (PG1) is a precursor of pepsin that correlates with maximal gastric acid output. Twenty years ago, researchers reported on 2 families who

"Familial hyperpepsinogenemia" and Helicobacter pylori infection.

Pepsinogen 1 (PG1) is a proenzyme precursor to pepsin, a protease secreted by the gastric chief cell. PG1 levels correlate with maximal gastric acid output. In 1979, Rotter et al. reported two pedigrees in which elevated PG1 levels and duodenal ulcers were prevalent. They proposed autosomal dominant inheritance of elevated PG1 and suggested that it was a risk factor for duodenal ulcer disease. In 1982, Helicobacter pylori (Hp) was discovered and was shown to be an important factor in peptic ulcer disease. Hp infection is also associated with increased PGI levels. We tested serum from one of the original pedigrees for Hp antibodies to determine whether Hp infection could explain the ulcers and elevated PG1 levels. ELISA tests were performed using the urease fraction of a crushed Hp extract. Banked serum from one of the original families was thawed and tested. Of the subjects, 90% (nine of 10) with elevated PG1 were seropositive for Hp, compared to only 31% (17 of 55) of those with normal PG1 levels (p < 0.001). The mean PG1 level was higher in the seropositive (94.1+/-13.3 ng/ml) than the seronegative subjects (54.8+/-3.6, p < 0.05). Three of the four subjects with ulcers were Hp-seropositive. The prevalence of Hp-seropositivity and elevated PG1 declined in parallel in each successive generation. When neither parent was seropositive, children were seronegative. The etiology of elevated PG1 levels in this pedigree is more likely due to Helicobacter pylori infection than to a genetic predisposition.

“familial hyperpepsinogenemia” and Helicobacter pylori infection

OBJECTIVE: Pepsinogen 1 (PG1) is a proenzyme precursor to pepsin, a protease secreted by the gastric chief cell. PG1 levels correlate with maximal gastric acid output. In 1979, Rotter et al. reported two pedigrees in which elevated PG1 levels and duodenal ulcers were prevalent. They proposed autosomal dominant inheritance of elevated PG1 and suggested that it was a risk factor for duodenal ulcer disease. In 1982, Helicobacter pylori (Hp) was discovered and was shown to be an important factor in peptic ulcer disease. Hp infection is also associated with increased PGI levels. We tested serum from one of the original pedigrees for Hp antibodies to determine whether Hp infection could explain the ulcers and elevated PG1 levels. METHODS: ELISA tests were performed using the urease fraction of a crushed Hp extract. Banked serum from one of the original families was thawed and tested. RESULTS: Of the subjects, 90% (nine of 10) with elevated PG1 were seropositive for Hp, compared to only 31% (17 of 55) of those with normal PG1 levels ( p < 0.001). The mean PG1 level was higher in the seropositive (94.1 ± 13.3 ng/ml) than the seronegative subjects (54.8 ± 3.6, p < 0.05). Three of the four subjects with ulcers were Hp-seropositive. The prevalence of Hp-seropositivity and elevated PG1 declined in parallel in each successive generation. When neither parent was seropositive, children were seronegative. CONCLUSIONS: The etiology of elevated PG1 levels in this pedigree is more likely due to Helicobacter pylori infection than to a genetic predisposition.

The effect of severe undernutrition, and subsequent refeeding on digestive function in human patients.

Severe undernutrition may adversely affect gut function. To investigate the effects of severe undernutrition and subsequent refeeding on human digestive function. Severely undernourished patients (body mass index (BMI) < 17 kg/m2) were studied before, and after a period of intensive nutritional support. Standard intestinal absorption tests (faecal fat and urinary xylose excretion), pentagastrin-stimulated acid secretion, and cholecystokinin octapeptide (CCK-8)-stimulated pancreatic enzyme secretion tests were performed. In addition, duodenal biopies were taken to assess gut mucosal morphology. Findings were evaluated in comparison to a group of normal healthy volunteers. Mean BMI of the patients prior to nutritional support was 13.41 kg/m2, with improvement to 16.12 kg/m2 after. Duodenal histology showed evidence of villous atrophy in six of 14 (43%) undernourished patients. Mean xylose excretion following a 5 g oral dose was 0.62 g/5 h in the group of undernourished patients prior to nutritional support (normal > 1 g/5 h), with improvement to 1.40 g/5 h (P < 0.01) after feeding. Maximal gastric acid output was significantly impaired in the undernourished group, as compared to the controls (6.94 mEq/l vs 25.53 mEq/l, P < 0.02), with a significant improvement to 12.30 mEq/l (P < 0.05) following nutritional support. Pancreatic enzyme output was significantly reduced (amylase 830.9 U/h vs 2304 U/h, P < 0.01; lipase 38.0 U/h vs 118.6 U/h, P < 0.01; trypsin 119.7 U/h vs 341.4 U/h, P < 0.01). Following a period of nutritional support there was a significant improvement in amylase and lipase outputs to 1819 U/h and 85.5 U/h, respectively (P < 0.01). These levels were not significantly different from the normal controls. Trypsin output, however, remained significantly impaired at 174.3 U/h (P < 0.01). Severe undernutrition is associated with significant impairment of digestive function, with improvement occurring following nutritional support. These changes may affect initial tolerance to enteral feeding, particularly in those patients with co-existent gut disease.

Antigastric Autoantibodies and Gastric Secretory Function in Helicobacter pylori-Infected Patients with Duodenal Ulcer and Non-Ulcer Dyspepsia

Background: Autoantibodies against epitopes located at the canaliculi of human parietal cells occur in about 30% of Helicobacter pylori-infected patients. This has led to the hypothesis that gastric secretory function could be inhibited by anticanalicular autoantibodies in H. pylori gastritis. Methods: Forty-four H. pylori-infected patients with and without duodenal ulcers were screened for anticanalicular autoantibodies by means of immunohistochemistry. Plasma gastrin levels and basal and maximal gastric acid output were determined. Results: Fasting gastrin levels were significantly increased in the group with anticanalicular autoantibodies. In the group of patients with non-ulcer dyspepsia the presence of anticanalicular autoantibodies was significantly correlated with an impaired basal acid secretion. Conclusions: Antigastric autoimmunity in H. pylori gastritis seems to be relevant for gastric hyposecretion either directly by inhibiting the proton pump or indirectly through the development of gastric mucosa atrophy.

Dietary linoleic acid, gastric acid, and prostaglandin secretion

Basal and pentagastrin-stimulated gastric acid secretion, fasting serum gastrin concentrations, and the gastric output of prostaglandin E and its major metabolite 13,14-dihydro 15-keto prostaglandin E2 were measured in 9 normal subjects before and after 14–20 days of dietary supplementation with linoleic acid. Mean maximal gastric acid output fell from 36.0 ± 3.3 (SEM) to 30.1 ± 2.9 mmol/h (p < 0.05), although mean basal acid output was not significantly affected (8.3 ± 2.1 and 7.2 ± 1.7 mmol/h, respectively). Mean fasting serum gastrin concentrations increased from 19.2 ± 3.1 to 30.9 ± 3.8 ng/L (p < 0.01) after linoleic acid, probably because of acid suppression. The mean output of prostaglandin E increased from 498 ± 110 to 1254 ± 465 ng/h (p < 0.05); that of its metabolite increased from 165 ± 18 to 1168 ± 645 ng/h (p < 0.01). These findings show that in normal subjects essential fatty acid weakly inhibits gastric acid secretion, but considerably increases gastric prostaglandin output.

Pre- and Postcholecystectomy Duodenogastric Reflux

The purpose of the study was to assess whether cholecystectomy is usually followed by increased duodenogastric reflux and whether there are subsequent changes in the histology of the gastric mucosa and in acid secretion. Eleven patients were submitted, before cholecystectomy and 6 months afterwards, to gastric aspirates, assay of bile acids in the gastric juice and gastroscopy with biopsies from the antral mucosa and the main body. Our results show a significant increase, after cholecystectomy, in the amount of duodenogastric reflux (p < 0.01). However, the total amount of bile acids present in the stomach do not seem to affect the inflammatory injury to the mucosa. Nine times out of eleven there was a reduction of maximal gastric acid output: again, this fact does not seem to be correlated to the amount of bile reflux. The authors conclude that, as already stressed by others, injury to the mucosa is less affected by the amount of bile acids flowing back into the stomach than by other important factors such as the duration of contact, gastric pH, the presence of other constituents in the duodenal juice (lysolecithin) and the type of bile acid that is actually present.

Elevated Serum and Antral Gastrin in Obese (ob/ob) Mice

Elevations in serum gastrin concentration of six to seven times were found in postabsorptive 5- and 10-wk-old, but not 30- and 40-wk-old, obese mice in comparison with the appropriate lean controls. At 10 wk of age a fourfold hypergastrinemia was also evident in (ob/ob) mice denied food for 48 h. In 10-wk-old (ob/ob) mice that had eaten the same amount of food as lean mice from weaning, serum gastrin was six times that of lean controls. Antral gastrin concentration was 54% higher in fed 10-wk-old (ob/ob) mice than in lean mice. No relationship was found between alterations in serum gastrin and measures of gastrointestinal size or proliferative status. Maximal gastric acid output, expressed with respect to oxyntic mucosal dry weight, was reduced by 52% in 10-wk-old (ob/ob) mice compared with lean controls. It is concluded that the hypergastrinemia of 10-wk-old (ob/ob) mice is not caused by hyperphagia, but may be a consequence of reduced acid inhibition of gastrin release.

Influence of age and stomach function on serum vitamin B12 concentration.

Serum vitamin B12 (B12), maximal gastric acid output (MAO), and B12 absorption were determined in 82 subjects, age 32 to 85 years, who had normal absorption of radiocyanocobalamin. In 46 of the patients the gastric intrinsic factor (IF) was also measured. Serum B12 concentration and MAO varied widely in all age groups from abnormally low to definitely normal. The mean values for serum B12 and MAO, however, declined very similarly with advancing age owing to an increased incidence of low values for these two measurerment in the aged. There was no significant fall in the mean B12 absorption or IF secretion as a function of old age. Achlorhydric and hypochlorhydric patients invariably had lower mean serum B12 concentrations than those with adequate MAO. Conversely, patients with normal MAO all had normal serum B12 levels. Serum B12 concentration, although correlating with both MAO and IF secretion, showed a closer relationship to the former than to the latter. These findings suggest that the stomach, aside from producing the IF, plays an important role in maintaining a normal serum B12 concentration.

Effect of parapenzolate bromide (Relanol) on the gastric acid secretion of patients with peptic ulceration.

Summary: The basal and maximal gastric acid output were determined before and during maintenance therapy with long-acting parapenzolate bromide (Relanol) in 15 Chinese male subjects suffering from peptic ulceration. Statistical analysis of the results confirmed that there was significant suppression of both basal and maximal acid secretion by parapenzolate bromide. No untoward side effects, other than dryness of the mouth, were seen. It is concluded that parapenzolate bromide is a safe and effective anticholinergic drug.

Gastrin: obligatory intermediate for activation of gastric histidine decarboxylase in the rat.

ARTICLESGastrin: obligatory intermediate for activation of gastric histidine decarboxylase in the ratD Aures, LR Johnson, and LW WayD Aures, LR Johnson, and LW WayPublished Online:01 Jul 1970https://doi.org/10.1152/ajplegacy.1970.219.1.214MoreSectionsPDF (753 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByThe effect of the histidine decarboxylase inhibitor brocresine (NSD-1055) on gastric acid secretion in rats12 April 2011 | Journal of Pharmacy and Pharmacology, Vol. 23, No. 6The effect of submaximal doses of pentagastrin on gastric acid secretion, histamine and histidine decarboxylase in rats12 April 2011 | Journal of Pharmacy and Pharmacology, Vol. 25, No. 3The Role of the Antrum and the Vagus Nerve in the Metabolism of Histamine in the Human Gastric Mucosa8 July 2009 | Scandinavian Journal of Gastroenterology, Vol. 26, No. 8Trophic Effects of Gut Peptides1 January 2011Inhibition of histamine biosynthesis and gastric function in the rat: effect on pentagastrin-induced gastric acid secretionAgents and Actions, Vol. 13, No. 2-3The Myogenic Response1 January 2011Restraint-induced stress ulcer. II. biochemical and ultrastructural studies of gastric mucosaWorld Journal of Surgery, Vol. 4, No. 1Pharmacological ActionsGastrin: Obligatory intermediate in the postprandial mobilization of gastric histamine in the ratExperientia, Vol. 33, No. 11The Role of Cholinergic Excitation in the Formation of Histamine within the Rat Gastric MucosaActa Physiologica Scandinavica, Vol. 97, No. 2Gastric acid secretionThe American Journal of Digestive Diseases, Vol. 21, No. 5Is the basal activity of rat stomach histidine decarboxylase affected by antrectomy?Experientia, Vol. 31, No. 12Histamine and its metabolism in mammals part II: Catabolism of histamine and histamine liberationAgents and Actions, Vol. 5, No. 3Action of Insulin on Some Other Organs and on DifferentiationEndocrine Cells of the Gastric MucosaGastrinACTIVATION OF HISTIDINE DECARBOXYLASE BY H2-RECEPTOR BLOCKADE: MECHANISM OF ACTION19 July 2012 | British Journal of Pharmacology, Vol. 53, No. 1Use of radiorespirometry to evaluate in rats the effects of feeding and fasting on the decarboxylation of 14C histidineThe American Journal of Surgery, Vol. 126, No. 5Secretin and Cholecystokinin (CCK)Effect of pentagastrin and feeding on gastric histidine decarboxylase activity in the antrectomized ratEuropean Journal of Pharmacology, Vol. 18, No. 1The activation of rat stomach histidine decarboxylase is independent of the histamine levelExperientia, Vol. 27, No. 11The regulation of gastric histidine decarboxylase activity: II. Effects of physiological stimuli during pyridoxine deficiencyLife Sciences, Vol. 10, No. 21Activation of rat stomach histidine decarboxylase after inhibition of acid secretion with 2-Phenyl-2-(2-Pyridyl)-Thioacetamide (SC-15396)Experientia, Vol. 27, No. 9Mechanism of activation of rat stomach histidine decarboxylase after vagal denervationEuropean Journal of Pharmacology, Vol. 16, No. 1Control of Gastric Secretion: No Room for Histamine?Gastroenterology, Vol. 61, No. 1Effect of Pentagastrin on Maximal Gastric Acid Output in Rats with Gastric Fistulas27 September 2008 | Archives Internationales de Physiologie et de Biochimie, Vol. 79, No. 3 More from this issue > Volume 219Issue 1July 1970Pages 214-216 Copyright & PermissionsCopyright © 1970 by American Physiological Societyhttps://doi.org/10.1152/ajplegacy.1970.219.1.214PubMed5424847History Published online 1 July 1970 Published in print 1 July 1970 Metrics

Estimation of maximal gastric acid secretory capacity after augmented histamine stimulation.

One hundred and eighty-two patients with gastroduodenal diseases and 35 healthy subjects were examined with the augmented histamine test, and five normal volunteers were examined after maximal subcutaneous and intravenous histamine stimulation in a total of 43 tests and dose-response experiments. The different estimates of the maximal gastric acid output in the augmented histamine test and the histamine infusion test are compared.In clinical practice, the augmented histamine response, calculated from the 15-45-minute period of the augmented histamine test with subcutaneous stimulation, offers a valid, repeatable, and efficient estimate of the calculated maximal acid secretory capacity and the parietal cell mass, not surpassed by any other estimate, calculated from other 15-minute outputs or with use of other gastric secretory stimulants. It is recommended that the augmented histamine response calculated from the 15-45-minute period of the augmented histamine test with subcutaneous stimulation should be us...

Effect of Antrectomy, Vagotomy with Gastrojejunostomy, and Antrectomy with Vagotomy on the Spontaneous and Maximal Gastric Acid Output in Man

Effect of Antrectomy, Vagotomy with Gastrojejunostomy, and Antrectomy with Vagotomy on the Spontaneous and Maximal Gastric Acid Output in Man