Gastric Acid Secretory Function Research Articles

T1075 Comparison of Acid-Suppressive Effects of Three Brands of Generic Lansoprazole with Original Lansoprazole: Pharmacodynamic Equivalence Is Not Necessarily Guaranteed By Pharmacokinetic Bioequivalence Tests

G A A b st ra ct s others [55.4 (30.6-71.7) ng/mL in GU-M and 24.1 (16.7-59.2) ng/mL in GU-U, respectively]. Consequently, the more proximal the ulcer located in the stomach, the lower the PGI/PGII ratio was; 4.15 (3.51-5.00) in DU, 5.09 (4.13-6.40) in GU-P, 3.46 (2.70-4.12) in GU-A, 3.12 (2.70-3.45) in GU-L, 2.70 (2.37-3.79) in GU-M, and 1.80 (1.38-2.43) in GU-U. 7/65 (10.8%), 3/65 (4.6%) and 0/65 (0.0%) in DU, 1/9 (11.1%), 0/9 (0.0%) and 0/9(0.0%) in GU-P, 12/48(25.0%), 6/48(12.5%) and 0/48(0.0%) in GU-A, 3/12 (25.0%), 1/12 (8.3%) and 0/12 (0.0%) in GU-L, 11/21 (52.4%), 9/21 (42.9%) and 0/21 (0.0%) in GU-M, and 14/17 (82.4%), 12/17 (70.6%) and 9/17 (52.9%) in GU-U, were compatible with each of the three respective criteria in screening tests of subjects at high-risk for gastric cancer; PGI ≦ 70 ng/mL and PGI/PGII ratio ≦ 3.0, PGI ≦ 50 ng/mL and PGI/PGII ratio ≦ 3.0, and PGI ≦ 30 ng/mL and PGI/PGII ratio ≦ 2.0. CONCLUSIONS: PGI and the PGI/PGII ratio correlated well with the location of an ulcer. It is thought that patients with an ulcer in the middle body or more proximal differ from those with more distally located one, when considering gastric acid secretory function and gastric cancer risk.

Role of ghrelin in the regulation of gastric acid secretion involving nitrergic mechanisms in rats

Ghrelin, an endogenous ligand for growth hormone secretagogue receptor (GHS-R), has been identified in the rat and human gastrointestinal tract. Ghrelin has been proposed to play a role in gastric acid secretion. Nitric oxide (NO) was shown as a mediator in the mechanism of ghrelin action on gastric acid secretory function. However, there is a little knowledge about this topic. We have investigated the role of ghrelin in gastric acid secretion and the role of NO as a mediator. Wistar albino rats were used in this study. The pyloric sphincter was ligated through a small midline incision. By the time, saline (0.5 ml, iv) was injected to the control group, ghrelin (20 microg/kg, iv) was injected to the first experimental group, ghrelin (20 microg/kg, iv) + L-NAME (70 mg/kg, sc) was injected to the second group and L-NAME (70 mg/kg, sc) was administered to the third group. The rats were killed 3 h after pylorus ligation; gastric acid secretion, mucus content and plasma nitrite levels were measured. Exogenous ghrelin administration increased gastric acid output, mucus content and total plasma nitrite levels, while these effects of ghrelin were inhibited by applying L-NAME. We can conclude that ghrelin participates in the regulation of gastric acid secretion through NO as a mediator.

HELICOBACTER PYLORI GASTRITIS AND GASTRIC PHYSIOLOGY

It is now recognized that Helicobacter pylori infection exerts profound and diverse effects on gastric acid secretory function and that the alterations in acid secretion depend on the pattern of gastritis caused by the infection. In patients with an antral predominant nonatrophic gastritis, there is acid hypersecretion leading to duodenal ulcer disease. In patients with an atrophic pangastritis, there is markedly reduced acid secretion and increased risk for gastric cancer. It is now recognized that acid secretion also modifies H. pylori gastritis and a person's premorbid acid secretory status may be an important factor in determining the pattern of gastritis that an individual develops. This two-way interaction between H. pylori gastritis and gastric acid secretion is important in understanding the role of H. pylori infection in the response to proton-pump inhibitor therapy: It explains the more profound control of gastric acid secretion in H. pylori-positive patients and why rebound acid hypersecretion is confined to H. pylori-negative subjects.

Gastric ECL-cell hyperplasia produces enhanced basal and stimulated gastric acid output but not gastric erosion formation in the rat

1. 1. The purpose of this study was to examine the change in gastric acid output and gastric erosion formation produced by inducing gastric enterochromaffinlike (ECL) cell hyperplasia in female rats. 2. 2. Rats were treated with vehicle or ranitidine (1,200 μmol/kg/day×4 wks) administered via SC Alzet minipumps. Experiments were performed 24 hours after removing the minipump, when the inhibitory effect of ranitidine on gastric acid secretion had been lost. 3. 3. Basal gastric acid secretion was 7-fold higher in chronic ranitidine animals than in sham control. 4. 4. Both total and net gastric acid secretions stimulated by carbachol/pentagastrin infusion or histamine injection were significantly higher in chronic ranitidine animals than in controls. 5. 5. By contrast, intracisternal injection of the chemical vagal stimulant RX77368 (100 ng) resulted in no net increase in acid output of the recovered ranitidine-pretreated group. 6. 6. No significant changes in gastric erosions produced experimentally by cold exposure plus restraint or indomethacin pretreatment were noted in recovered chronic ranitidine animals compared to sham controls. 7. 7. These findings suggest that achlorhydria-induced ECL cell hyperplasia augments both basal and stimulated gastric acid secretory function. The histamine results implicate an enhanced parietal cell mass, upregulation of H 2 receptors, and/or second-messenger events at the parietal cell as the mechanism for the enhanced gastric secretory response.

8-OH-DPAT stimulates gastric acid secretion through a vagal-independent, adrenal-mediated mechanism

Serotonin (5-hydroxytryptamine, 5-HT) is a neuroendocrine component of the gastrointestinal tract. 5-HT 1A receptors exist both in the brain and have been demonstrated autoradiographically in high density in the rat stomach. However, the physiologic role of 5-HT 1A receptors in modulating gastric function is not known. The effect of the selective 5-HT 1A receptor agonist, (±)-8-hydroxy-2-( n-dipropylamino)tetralin (8-OH-DPAT), on gastric acid secretory function was compared to 5-HT in acute, urethane-anesthetized gastric-fistulated rats during pentagastrin infusion. 5-HT inhibited, but 8-OH-DPAT stimulated, gastric acid secretion in a dose-dependent manner. Bilateral cervical vagotomy or celiac ganglionectomy did not reverse the effect of 8-OH-DPAT on acid secretion. However, the enhancement of acid by 8-OH-DPAT was attenuated by acute adrenalectomy or close intra-arterial administration of spiperone, but not idazoxan. Thus, the data suggest that the selective 5-HT 1A receptor agonist 8-OH-DPAT may augment gastric secretory function via an adrenal-dependent mechanism.

Effect of enteral feeding on the maintenance of gastric acid secretory function: P. E. Hyman, E. J. Feldman, M. E. Ament, et al. Gastroenterology 84:341–345, (February), 1983

Effect of enteral feeding on the maintenance of gastric acid secretory function: P. E. Hyman, E. J. Feldman, M. E. Ament, et al. Gastroenterology 84:341–345, (February), 1983

Effect of Enteral Feeding on the Maintenance of Gastric Acid Secretory Function

The effects of enteral feeding on the maintenance of gastrointestinal function in human infants are unknown. The effects of enteral feeding on gastric acid secretory function were studied by investigating three groups of infants: infants fed normally, infants with gastrointestinal disease fed by a combination of enteral and parenteral means, and infants fed by total parenteral nutrition. In 14 infants with gastrointestinal disease fed with total parenteral nutrition for a mean of 7 mo (range 1.5-24 mo), basal gastric acid secretion and pentagastrin-stimulated maximal gastric acid secretion were significantly less than in 26 normal infants (p less than 0.01) and in 11 infants with gastrointestinal disease nourished with a combination of enteral and parenteral feeding (p less than 0.01). In each of seven infants fed with total parenteral nutrition for a mean of 5 mo (range 1.5-10 mo), basal and maximal gastric acid secretion increased after a 6-8-wk trial of enteral feeding, a highly significant difference. In one infant, the ability to secrete normal amounts of acid in response to pentagastrin (achieved after an initial trial of enteral feeding) was lost after a 4-mo enteral fast, but returned after a second trial of enteral feeding. These results demonstrate that, in human infants, enteral feedings are necessary for normal oxyntic mucosal secretory function.

Effects of prostaglandin E2 on gastric acid secretory function and ulcerogenesis induced by different methods (experimental study).

This experimental study was designed to determine the effects of different doses of prostaglandin E2 on gastric acid secretory function and ulceration in rats. Ulceration was induced by the method of Shay on 81 rats and by the method of stress on 114 rats. Ninety-seven rats were included in the experimental group, 98 rats constituted the control one. It has been established that three subcutaneous injection of prostaglandin E2 at the single dose of 540 μg per kg of body weight were found to have a marked inhibitory effect of this drug on the gastric juice volume, titration activity of free hydrochloric acid and total acidity. Distinct protective effects of this drug on the course of experimental ulcer were detected as well. Similar subcutaneous injections of prostaglandin E2 at the single dose of 180 μg per kg had no apparent inhibitory effect on the parameters mentioned. The studies of prostaglandin E2 action at the doses of 360, 1080 and 1800 μg per kg on ulceration induced by the combination of stress and intraperitoneal injections of histamine (at the dose of 7.5 mg/kg of body weight) were carried out. The results of these investigation showed the subcutaneous injections of Pg E2 at the dose of 1800 µg per kg to have a protective effect on the gastric mucosa.

Clinical studies on the circadian variation of blood gastrin levels

Circadian variations of blood gastrin levels at 4-hour intervals for 24 hours were studied in patients with peptic ulcer and in healthy control subjects under non-stimulated conditions directly before each meal and during the night time. The variation patterns were classified into 4 groups; Type A which showed little variation of blood gastrin levels during whole day and were divided into Type A-l having higher gastrin level and Type A-2 having lower gastrin level, Type B which showed a single peak value during the day-time, Type C which showed two or more peak values within the whole day, and the group of unclassifiable patterns. These patterns were found to be correlated with the disease states of gastric and duodenal ulcers, especially with gastric acid secretory function. Discussions were made on the circadian variation patterns of the blood gastrin levels in connection with some other pathological physiological results obtained during the studies.