Acid Secretion In Healthy Subjects Research Articles

Esomeprazole inhibits the pentagastrin-stimulated secretion of gastric acid in healthy Japanese volunteers.

Gastroesophageal reflux disease (GERD) is a common disease, in which the reflux of gastric acid causes mucosal damage of the esophagus and/or troublesome symptoms. Esomeprazole, a proton pump inhibitor, has been used for treatment of GERD in Japan since 2011; namely, only little is known about its effect on gastric acid secretion in Japanese. We, therefore, assessed the relationship between dose and timing of esomeprazole administration and gastric acid inhibition in 11 healthy male Japanese volunteers by directly examining gastric acid secretion capacity. In this randomized, open-label, three-way crossover study, the subjects were dosed with esomeprazole 10 mg or 20 mg once a day (q.d.), or 20 mg twice a day (b.i.d.) for 14 days, and pentagastrin-stimulated gastric acid secretion was measured by endoscopic gastrin test. At steady states, gastric acid inhibition rates were significantly higher in esomeprazole 20 mg b.i.d. (median 100.0%, interquartile range [IQR] 99.4-100%, P = 0.027) or 20 mg q.d. (100.0%, IQR 99.7-100%, P = 0.016), compared with 10 mg q.d. (98.4%, IQR 84.4-100%). At trough states, esomeprazole 20 mg b.i.d. showed significantly higher gastric acid inhibition (99.6%, IQR 99.0-100%) than did 20 mg q.d. (84.2%, IQR 76.4-88.8%, P = 0.002) or 10 mg q.d. (64.9%, IQR 59.1-76.7%, P = 0.001). Thus, esomeprazole 20 mg b.i.d. was sufficient to inhibit > 99% gastric acid secretion in healthy subjects. We propose that esomeprazole 20 mg b.i.d. is effective for treating Japanese patients with refractory GERD who require long-lasting gastric acid inhibition.

Effects of low-dose cimetidine on nocturnal acid secretion in healthy subjects

The effects of 100 mg and 200 mg bedtime doses of cimetidine on nocturnal gastric acid secretion were examined in nine healthy subjects in a double blind, placebo controlled, randomised three way crossover study. Treatment was given at 23.00 hours and the gastric contents continually aspirated from midnight until 07.00 hours the following morning. Hourly aliquots were analysed for pH and acid output. Relative to placebo the 100 mg and 200 mg doses of cimetidine respectively increased mean pH by 2.22 and 2.63 units/h (P less than 0.001) with mean acid output decreasing by 0.95 and 0.98 mmol/h (P less than 0.001). Whilst mean pH was higher and mean acid output was lower for 200 mg cimetidine compared to 100 mg cimetidine the difference was not statistically significant. Mean hourly pH was consistently above pH 3 for 100% of the time for both doses of cimetidine whereas mean pH failed to reach this value at anytime on placebo. Low doses of cimetidine taken at bedtime effectively reduced nocturnal gastric acid secretion in healthy individuals.

Pantoprazole affords long-term inhibition of pentagastrin-stimulated gastric acid secretion in healthy subjects

Pantoprazole affords long-term inhibition of pentagastrin-stimulated gastric acid secretion in healthy subjects

Meal-stimulated gastric acid secretion in healthy subjects correlates with postprandial but not fasting gastric acidity

A partially purified pregastric lipase from lambs was used as a catalyst for the hydrolysis of tributyroylglycerol. The reaction was followed by pH-stat autotitration of the released butyric acid. Integral values for pH and temperature were selected for determination of full Michaelis-Menten plots, and a kinetic surface was derived to characterize the activity of the enzyme preparation over a wide combination of these conditions. This surface enclosed a region of maximum activity centered on optimal pH (pH 6.4) and temperature (43°C), although optima were not sharply delineated. The activity in the surrounding region was generally high, and the value of the Michaelis-Menten constant was < 0.2 mM, indicating that tributyroylglycerol was generally a highly favored substrate.

Eradication of Helicobacter pylori restores the inhibitory effect of cholecystokinin on postprandial gastrin release in duodenal ulcer patients.

Helicobacter pylori infection may be associated with duodenal ulcer (DU) and accompanied by enhanced gastrin release but the mechanism of this H pylori related hypergastrinaemia in DU patients is unclear. Cholecystokinin (CCK) has been implicated in the feedback control of gastrin release and gastric acid secretion in healthy subjects. This study therefore investigated if CCK participates in the impairment of postprandial gastrin release and gastric secretion in six DU patients. Tests were undertaken with and without elimination of endogenous CCK by loxiglumide, a selective CCK-A receptors antagonist, before and after eradication of H pylori with triple therapy (omeprazole, amoxicyllin, bismuth). In H pylori positive DU patients, the post-prandial decline in pH (with median pH 3.5) was accompanied by a pronounced increment in plasma gastrin but the administration of loxiglumide did not affect significantly this postprandial rise in plasma gastrin and gastric pH profile. After eradication of H pylori, the plasma gastrin concentration was reduced while the median postprandial pH was significantly increased (median pH 4.3). The administration of loxiglumide resulted in significantly greater increase in postprandial plasma gastrin and greater decrease in pH (median pH 3.1) in these patients. This study shows that (a) infection with H pylori is accompanied by an enhanced gastrin release and gastric acidity in DU patients, (b) the failure of loxiglumide to affect plasma gastrin or gastric acid secretion in H pylori infected DU patients could be attributed, at least in part, to the failure of endogenous CCK to control gastrin release and gastric secretion by releasing somatostatin, and (c) the test with loxiglumide may be useful in the identification of patients with impaired feedback control of gastrin release and gastric secretion resulting from infection with H pylori.

Effect of sham feeding on gastric acid secretion in healthy subjects and duodenal ulcer patients: Evidence for increased basal vagal tone in some ulcer patients

Sham feeding augments gastric acid secretion by activating efferent vagal pathways to the stomach. If increased vagal activity in the basal state were the cause of increased basal acid secretion in some patients with duodenal ulcer, these patients might be expected to secrete little or no additional acid in response to sham feeding. To test this, we measured basal and sham feeding-stimulated acid secretion (as well as peak pentagastrin-stimulated acid output) in 29 duodenal ulcer patients and 22 healthy subjects. Four ulcer patients who had markedly increased basal acid secretion (basal/peak acid output > 0.30) and normal basal serum gastrin concentrations failed to augment acid secretion in response to sham feeding. On the other hand, patients with marked basal acid hypersection owing to hypergastrinemia (Zollinger-Ellison syndrome) responded to sham feeding with a large increase in acid secretion above basal rates. Every normal subject responded to sham feeding with an increase in acid secretion above basal rates, even when acid secretion had been stimulated by an intravenous pentagastrin infusion before beginning sham feeding. These findings suggest that in some patients with duodenal ulcer (4 of 29 in this study) increased basal acid secretion is caused by increased vagal tone.

The effect of antral distension in healthy subjects on betazole-stimulated gastric acid secretion and the plasma concentration of immunoreactive neurotensin.

Antral distension in seven healthy subjects had the same inhibitory effect, approximately 20% inhibition, on gastric acid secretion stimulated by pentagastrin and betazole (Histalog). The plasma concentration of neurotensin in peripheral venous blood was unchanged during antral distension in healthy subjects. The plasma concentration of neurotensin in portal blood was also unchanged during antral distension in anaesthetized duodenal ulcer patients and in non-ulcer patients. The inhibition of pentagastrin-stimulated gastric acid secretion by balloon distension of the antrum was unchanged by preceding intramuscular injection of metoclopramide. The inhibitory effect of antral distension on gastric acid secretion in healthy subjects does not seem to be mediated by secretin, cholecystokinin, bulbogastrone, neurotensin, or a dopaminergic mechanism.

Gastric Cyclic Nucleotide Concentration in Health and Disease: Response to secretagogues and role of circulating gastrin and intragastric acid secretion

Cyclic AMP and cyclic GMP concentrations were measured in suction biopsy specimens of gastric fundic and antral mucosa and in gastric juice in response to maximum stimulation by histamine (0.015 mg per kg per hr), betazole (1.5 mg per kg), and pentagastrin (6 μg per kg) in 14 normogastrinemic healthy subjects, in 46 patients with dyspepsia or peptic ulcer (PU) disease and normal serum gastrin levels, and in 14 patients with hypergastrinemia, including 8 with pernicious anemia (PA), 3 with Zollinger-Ellison (ZE) disease, and 3 with gastric carcinoma. No regional differences were noted in unstimulated gastric antral or fundic cyclic nucleotide content in normal subjects or patients. During secretagogue stimulation no significant changes in cyclic nucleotide concentrations were observed in antral or fundic mucosa of healthy subjects or patients. During basal hourly secretion, cyclic nucleotide concentration and output in gastric juice was relatively constant, suggesting a steady state of secretion. After secretagogue stimulation, the concentrations of cyclic AMP and cyclic GMP were reduced by at least 50% and correlated with the increased parietal volume output, suggesting a dilutional effect. There was no significant change in gastric juice cyclic nucleotide output except in PU subjects after betazole stimulation, in whom cyclic AMP production increased almost 2-fold. This change in gastric juice cyclic AMP appeared proportional to a greater parietal volume flow and did not reflect intracellular mucosal events. Similarly, a decreased concentration of cyclic AMP in the basal and stimulated gastric juice of ZE patients and a reduced cyclic AMP output in PA patients also appeared proportional to volume flow. The presence of cyclic AMP in unstimulated gastric juice in PA suggested, in part, a nonparietal origin for cyclic AMP, probably derived from interstitial fluid secretion or transmucosal exudation from plasma. It is concluded that intra- or extracellular gastric cyclic AMP or cyclic GMP concentrations are not modulated by secretagogue stimulation, circulating high gastrin levels, alteration in intraluminal pH, or increasing age. These studies fail to implicate cyclic nucleotides as intracellular mediators of stimulated gastric acid secretion in healthy subjects, PU disease PA, ZE disease or gastric carcinoma.

The Effect of Intragastric Neutralization on the Gastric Acid Response to Antral Distension in Man

The gastric acid secretion in response to graded antral distension was determined in healthy subjects and in peptic ulcer patients with water perfusion or alkaline buffer perfusion of the stomach, giving an intragastric pH of 1.8-3.0 and 6.2-8.3 respectively. Intragastric neutralization increased the basal acid secretion in healthy subjects and gastric ulcer patients but did not change the basal acid secretion in duodenal ulcer patients. Distension of the antrum produced the same secretory effect with and without intragastric neutralization: no increased acid response in healthy subjects, a slight acid response in patients with a quiescent duodenal ulcer or a gastric ulcer, and a more pronounced acid response in patients with an active ulcer, amounting to about 30% of the peak acid response to pentagastrin. The results show that: a) the peptic ulcer patients - and particularly patients with an active duodenal ulcer - are more sensitive to the acid secretory effect of antral distension than healthy subjects; b) increasing the intragastric pH above 20 does not enhance the acid response to antral distension; c) the acid secretory effect of antral distension is markedly less in man than the effect observed in the dog.