Phase Of Gastric Acid Secretion Research Articles

Biomedical gastronomy in the interventions of smell and taste disorders in ‘altered eating’

Biomedical gastronomy in the interventions of smell and taste disorders in ‘altered eating’

Potential adverse effects of proton pump inhibitors mimicking other conditions

Proton pump inhibitors, the most potent and safest acid inhibitory agents available, irreversibly bind and inhibit H+, K+-ATPase. They inhibit all phases of gastric acid secretion. Proton pump inhibitors are considered extremely safe and are regularly prescribed. They may, however, have side effects. They affect the clearance of other medicines. And the reactions to them may mimic other conditions and side effects of other medicines.

Gastric acid secretion induced by paraventricular nucleus microinjection of orexin A is mediated through activation of neuropeptide Yergic system

Very recently, we have reported that the modulatory effect of PVN on gastric acid secretion may be mediated through the orexin fibers and/or orexin-responsive neurons. In this study, we address the hypothesis which demonstrates the existence of a putative orexin A – neuropeptide Y Y1/Y5 receptors interaction to increase gastric acid secretion in pyloric-ligated conscious rats. Male Wistar rats were implanted with guide canula directed to the PVN and lateral ventricle. Intracerebroventricular (ICV) microinjections of GR-231118 (Y1 receptor antagonist) and CGP-71683 (Y5 receptor antagonist) on gastric acid secretion were considered. The effect of pretreatment with Y1 receptor antagonist, GR-231118, and Y5 receptor antagonist, CGP-71683, on PVN orexin A-induced acid secretion was assessed. Gastric acid secretion was measured using the pylorus-ligation method, and the amount of gastric acid was determined by titration with 0.01N NaOH to a pH of 7.0. Key results: ICV microinjections of GR-231118 and CGP-71683 decreased acid secretion by 25±0.05% and 67±0.02%, respectively. ICV microinjections of GR-231118 and CGP-71683 inhibited effects of PVN-injected orexin-A on acid secretion. We suggest that Y1 and Y5 receptors stimulate gastric acid secretion and the stimulatory effect of PVN orexin receptors on gastric acid secretion may be mediated via interactions, at least in part, through activation of Y1 and Y5 receptors. These neural pathways may play key roles in the orexinergic action of orexins in the cephalic phase of gastric acid secretion.

Drug interaction studies of H2-receptor antagonists with mefloquine, pyrimethamine and sulfadoxine

Fansimef is a new antimalarial schizontocide that contains mefloquine, pyrimethamine, and sulfadoxine with a weight ratio of 1:20:10. This antimalarial combination is highly active against multidrug-resistant strains of Plasmodium falciparum. H2-receptor antagonists (cimetidine, famotidine, and ranitidine) are reversible competitive blockers of histamine at H2-receptor and do not affect the H1-receptor. These are potent inhibitors of all phases of gastric acid secretion. They do so by binding to H2-receptors on the parietal cells of stomach. The effect of various dissolution mediums with respect to pH on these drug–drug interactions and in vitro availability reveals that availability of antimalarial drugs increased to a smaller extent in the presence of H2-receptors. The influence of temperatures on these interactions has been examined to elucidate the mechanism of these interactions. Antimalarial drugs could be administrated concurrently with H2-receptor antagonist (cimetidine and famotidine); however, ranitidine should not be given because availability was almost suppressed in the presence of antimalarial drugs.

The effect of the antihistamines on the antral phase of gastric acid secretion in dogs.

Journal Article The effect of the antihistamines on the antral phase of gastric acid secretion in dogs Get access R A Payne, R A Payne The University Department of Surgery, Royal Infirmary, Sheffield Search for other works by this author on: Oxford Academic Google Scholar F D Naylor, F D Naylor The University Department of Surgery, Royal Infirmary, Sheffield Search for other works by this author on: Oxford Academic Google Scholar A W Kay A W Kay The University Department of Surgery, Royal Infirmary, Sheffield Search for other works by this author on: Oxford Academic Google Scholar British Journal of Surgery, Volume 48, Issue 212, May 1961, Pages 683–686, https://doi.org/10.1002/bjs.18004821222 Published: 06 December 2005

Cephalic phase of acid secretion involves activation of medullary TRH receptor subtype 1 in rats.

Mechanisms involved in the cephalic phase of gastric acid secretion were studied in awake fasted rats with chronic gastric fistula and exposed to the sight and smell of chow for 30 min. Acid secretion was monitored using constant intragastric perfusion and automatic titration. Sham feeding induced a peak acid response reaching 82 +/- 7 micromol/10 min within 20 min compared with the average 22 +/- 2 micromol/10 min in controls. The sham-feeding response was abolished by intracisternal pretreatment with the TRH(1)-receptor antisense oligodeoxynucleotides or subcutaneous injection of atropine, whereas TRH(1) mismatch oligodeoxynucleotides had no effect. Serum gastrin was not altered by the sham feeding and increased by refeeding. Gastrin antibody did not block the rise in acid during sham feeding, although the net acid response was reduced by 47% compared with the control group. Glycine-gastrin antibody, indomethacin and nitro-l-arginine methyl ester had no effect. Atropine and gastrin antibody decreased basal acid secretion by 98 and 75%, respectively, whereas all other pretreatments did not. These results indicate that the cholinergic-dependent acid response to sham feeding is mediated by brain medullary TRH(1) receptors in rats.

Central and peripheral regulation of gastric acid secretion by peptide YY

Peptide YY (PYY) released postprandially from the ileum and colon displays a potent inhibition of cephalic and gastric phases of gastric acid secretion through both central and peripheral mechanisms. To modulate vagal regulation of gastric functions, circulating PYY enters the brain through the area postrema and the nucleus of the solitary tract, where it exerts a stimulatory action through PYY-preferring Y1-like receptors, and an inhibitory action through Y2 receptors. In the gastric mucosa, PYY binds to Y1 receptors in the enterochromaffin-like cells to inhibit gastrin-stimulated histamine release and calcium signaling via a pertussis toxin-sensitive pathway.

GRP and Pavlov's dogs

See article on page 23 The cephalic phase of gastric acid secretion has been a topic of great interest to physiologists and physicians since its description by Pavlov 100 years...

Inhibition of sham feeding-stimulated acid secretion in dogs by immunoneutralization of gastrin.

A monoclonal antibody to gastrin was used to study the role of circulating gastrin in mediating acid secretion stimulated by sham feeding in dogs. On separate days, four conscious, fasted, adult mongrel dogs with esophageal and gastric fistulae were pretreated intravenously with either 7 mg of gastrin monoclonal antibody (MAb 28.2), 7 mg of keyhole limpet hemocyanin monoclonal antibody as control, or 12.5 micrograms/kg atropine sulfate. Thirty minutes later, acid secretion was stimulated first by sham feeding for 5 min, then, 60 min later, by an intravenous infusion of a maximum stimulatory dose of histamine (40 micrograms/kg) for 60 min, and after returning to basal, by intravenous infusion of a submaximal stimulatory dose of gastrin (200 pmol.kg-1.h-1) for 60 min. Acid output from secretions collected every 15 min by gravity drainage was determined by titration to pH 7.0 with 0.2 N NaOH. Sham feeding-stimulated acid output (17.7 +/- 5.5 mmol/h) was significantly inhibited by administration of either MAb 28.2 (0 mmol/h) or atropine (1.7 +/- 1.1 mmol/h). Histamine-stimulated acid output (19.6 +/- 3.4 mmol/h) was not reduced by either pretreatment. Gastrin-stimulated acid output (3.9 +/- 0.6 mmol/h) was significantly reduced only by pretreatment with MAb 28.2 (0.1 +/- 0.1 mmol/h) and not by atropine (2.2 +/- 1.4 mmol/h). A background intravenous infusion of pentagastrin (0.5 microgram.kg-1.h-1) restored sham feeding-stimulated acid output blocked by administration of MAb 28.2, although the intrinsic acid response to sham feeding could not be seen with the background pentagastrin infusion. Furthermore, the plasma gastrin response to sham feeding was not blocked by atropine pretreatment. Because immunoneutralization of both gastrin and cholinergic blockade significantly inhibited acid output during sham feeding, circulating gastrin and cholinergic pathways are involved in mediating the cephalic phase of gastric acid secretion in dogs.

Role of vagus nerves and gastrin in the gastric phase of acid secretion in male anesthetized rats.

We used the pylorus ligation model to determine the role of vagus nerves and gastrin in acid secretion induced by mechanical and chemical stimulation of the gastric lumen in anesthetized male rats. Gastric distension induced by intragastric instillation of saline resulted in a 17-fold increase in acid secretion over the basal level without an alteration in serum gastrin levels. Distension-stimulated acid secretion was inhibited by bilateral subdiaphragmatic vagotomy but not by CI-988, a gastrin receptor antagonist. Intragastric peptone produced a 71-fold increase in acid secretion over the basal level that was accompanied by a significant increase in serum gastrin levels. Whereas vagotomy almost abolished peptone-stimulated acid secretion, CI-988 inhibited peptone-stimulated acid secretion by only 50%. We conclude that the vagus nerves mediate acid secretion by mechanical and chemical stimulation and that gastrin mediates acid secretion partly by chemical stimulation but not by mechanical stimulation in anesthetized male rats.

Importance of vagus nerves in duodenal acid neutralization in anesthetized pigs.

During the cephalic phase of gastric acid secretion, vagally mediated synchronous stimulation of bicarbonate provides protection against the acid. The purpose of this study was to determine simultaneously the effect of electrical vagal stimulation (EVS) on pancreatic, hepatic, and duodenal mucosal bicarbonate secretion, thereby estimating their relative importance in vagally induced duodenal acid neutralization. Splanchnicotomy increased vagally induced pancreaticobiliary bicarbonate secretion, whereas duodenal mucosal bicarbonate secretion was unchanged. After splanchnicotomy, EVS (10 ms, 15 mA, 12 Hz) significantly increased pancreatic bicarbonate secretion (0-4.17 mmol/h), hepatic bicarbonate secretion (0.16 to 0.22 mmol/h), and duodenal mucosal bicarbonate secretion (0.17 to 0.31 mmol/h). Pancreaticobiliary bicarbonate secretion was atropine resistant, whereas vagally induced duodenal mucosal bicarbonate secretion was diminished by atropine (2.0 mg/kg). After splanchnicotomy, EVS (10 ms, 15 mA, 12 Hz) had no effect on portal plasma concentration of secretin, whereas vasoactive intestinal peptide was increased (14-29 pM). EVS at 12 Hz with varying duration (3 or 10 ms) and amplitude (3-50 mA) had no further effect on the bicarbonate secretion from the three organs. In addition, biliary [14C]mannitol clearance was shown not to be a reliable marker of canalicular bile secretion in pigs. These results suggest that in the anesthetized pig 1) vagal stimulation is only of minor importance to hepatic bicarbonate secretion; 2) vagal stimulation activates pancreatic bicarbonate secretion through both cholinergic muscarinic and noncholinergic transmission; and 3) vagal stimulation induces duodenal mucosal bicarbonate secretion mainly through cholinergic muscarinic transmission. In conclusion, these results suggest that only pancreatic and duodenal bicarbonate production play a role in vagally induced duodenal acid neutralization.

Gastrointestinal hormones, growth factors, and neurotransmitters

Growth factors regulate mucosal growth and adaptation to mucosal injury and intestinal resection. A number of peptide growth factors have been identified, including epidermal growth factor, transforming growth factor-α, insulinlike growth factor-l, and fibroblast growth factors. A series of articles are reviewed which emphasize that a number of peptide growth factors promote epithelial cell proliferation in response to injury. These studies provide some initial insights into mechanisms involved in ulcer healing. Understanding of physiologic events in the gastric and intestinal phases of gastric acid secretion have been aided by specific peptide receptor antagonists and monoclonal antibodies capable of neutralizing circulating peptide hormones. Application of these techniques has revealed that gastrin is a principal mediator of meal-stimulated acid secretion. Furthermore, somatostatin and cholecystokinin have been shown to inhibit gastric acid secretion when acid and fat, respectively, are introduced into the intestine. The concept of nonadrenergic noncholinergic inhibitory neural mechanisms has been reconfigured with the demonstration that nitric oxide is capable of inhibiting gastrointestinal smooth muscle and acting as a mediator of vasodilatation. It is clear that nitric oxide is an important inhibitory neurotransmitter and cell-derived mediator within the gastrointestinal tract.

Role of gastrin, histamine, and acetylcholine in the gastric phase of acid secretion in anesthetized rats.

To determine the relative contributions of gastrin, histamine, and cholinergic stimulation to the gastric phase of acid secretion, peptone-stimulated acid output was measured in urethan-anesthetized pylorus-ligated rats after intravenous administration of gastrin monoclonal antibody, cimetidine, and atropine. Intragastric peptone stimulated acid secretion four-fold over basal, which was associated with a significant increase in plasma gastrin levels. Gastrin immunoneutralization and simultaneous H2- and muscarinic-receptor blockade demonstrated that approximately 40% of peptone-stimulated acid output as attributed to endogenous gastrin through a histamine-dependent pathway, whereas 20% of acid output was accounted for by a cholinergic component. Another 10% of titratable acid was omeprazole-insensitive and presumably due to intragastric digestion of peptone. Therefore, approximately 30% residual acid output in response to peptone could not be accounted for by known acid stimulatory mechanisms. In rats given somatostatin monoclonal antibody to block the tonic inhibitory effect of endogenous somatostatin, residual acid output was a similar fraction of meal-stimulated acid output. In contrast, gastric distension induced by intragastric instillation of saline stimulated acid secretion to 1.5-fold over basal. Although 60% of distension-induced acid secretion could be inhibited by either H2 blockade or gastrin immunoneutralization, acid output returned to basal levels after simultaneous muscarinic blockade. These results indicate that gastrin, through a histaminergic pathway, is the principal mediator of meal-stimulated acid secretion in anesthetized rats. Approximately 30% of acid output was due to other unidentified mechanisms, such as chemical secretagogues, a direct effect of amino acids, or novel peptides.

Food coloring and monosodium glutamate: effects on the cephalic phase of gastric acid secretion and gastrin release in humans

Although food additives may have a significant impact on the marketing and acceptability of food and may occasionally lead to side effects, the effect of these additives on the digestive process in humans is unknown. We evaluated whether adding coloring or monosodium glutamate to food increases the cephalic phase of gastric acid secretion or gastrin release. When ordinary food coloring or unusual food coloring was added, acid secretion and gastrin release were similar to a control study with no food coloring added. Moreover, addition of 360 mg monosodium glutamate to beef consomme soup had no effect on the acid secretory or gastrin response to the meal. Thus, the food additives studied led to no objective alteration in the gastric exocrine or endocrine response to food.

Influence of Jejunal Hypertonic Glucose Infusion on Sham-Feeding-Stimulated Gastric Acid Secretion: Evidence of a Defective Mechanism in Duodenal Ulcer Patients

The aims of the present study were to determine in 14 healthy subjects and 14 duodenal ulcer patients the reproducibility of the acid secretory response to a modified sham-feeding test and the effect on this response of intrajejunal hypertonic glucose instillation, in order to evaluate the possibility of the existence of a defective inhibition of the cephalic phase of gastric acid secretion in duodenal ulcer disease. The reproducibility of the acid secretory response to a modified sham-feeding test was demonstrated in both groups in two consecutive tests. The hypertonic glucose instillation produced a significant inhibition of the acid secretory response to modified sham feeding only in the healthy subjects, suggesting that duodenal ulcer patients may have a defective mechanism of acid inhibition during vagal stimulation by modified sham feeding. Non-significant changes were observed in plasma gastrin and pancreatic glucagon levels.

Gastrin is a major mediator of the gastric phase of acid secretion in dogs: Proof by monoclonal antibody neutralization

We developed a monoclonal antibody, 28.2, that binds specifically to the amidated carboxyl terminal region common to gastrin and cholecystokinin. This immunoglobulin G1 antibody has high affinity (ID50 = 30–70 pM for gastrin and cholecystokinin peptides), binds labeled gastrin similarly at 37 °C and 4 °C, and shows minimal inhibition of binding in the presence of 40% canine serum. Antibody 28.2 was used to carry out in vivo immunoneutralization studies in 8 dogs previously prepared with chronic gastric fistulas. Preliminary studies revealed that a single intravenous dose of 0.75 mg of partially purified immunoglobulin G of monoclonal antibody 28.2 completely inhibited the acid stimulatory effect of exogenous gastrin-17 given intravenously at 200 pmol/kg · h, a physiologic dose, and inhibited by 70% the acid response to a supraphysiologic dose, 800 pmol/kg · h. The same dose of antibody decreased the acid secretory response obtained during distention of the stomach with 300 ml of 5.8% glucose solution by 98% and decreased the response to distention with 300 ml of 8% peptone solution by 68%. A 10-fold higher dose of antibody decreased the acid response to peptone by 96%. The gastrin antibody had no effect on the acid response to exogenous histamine. A control antibody, specific for the biologically inactive glycine-extended gastrin/cholecystokinin peptapeptide region, had no significant effect on gastric acid secretion stimulated by gastrin or by gastric distention with nutrients. These studies indicate that circulating gastrin is of major importance in the gastric phase of gastric acid stimulation caused by distention of the stomach with nutrients.

Peptides as regulators of gastric acid secretion.

Several peptides are important regulators of gastric acid secretion. The best characterized is gastrin. This circulating hormone is produced in the gastric antrum and mediates the gastric phase of acid secretion. Somatostatin is important as an inhibitory regulator of acid secretion, but the relative importance of paracrine versus endocrine delivery to its targets remains to be determined. The mammalian bombesin peptides, GRP27 and GRP10, probably are mediators of neural release of gastrin. Opioid peptides in the gastric wall appear to act as endogenous neurostimulants of gastric acid secretion under some conditions. Other neuropeptides in the gastric mucosa and submucosa, including sensory neuropeptides, may be important regulators of acid secretion. Hormones or nerves activated by fat and other substances in the lumen of the small intestine cause inhibition of acid secretion, but the specific peptides responsible for this effect have not yet been identified from a long list of candidates. The effects of peptides on the parietal cell and the gastrin and somatostatin cells are functionally linked with those of cholinergic and adrenergic nerves and with locally released histamine.

Gastric acidification inhibits meal-stimulated gastric acid secretion after prostaglandin synthesis inhibition by indomethacin in humans

The effects of cyclooxygenase inhibition by indomethacin on gastric acid secretion were studied in 8 healthy men. Oral doses of indomethacin (200 mg), administered 15 and 2 h before testing, were known to inhibit prostaglandin synthesis by 90% in 3 of the subjects as determined by prostaglandin E2 generation assay on endoscopically obtained gastric mucosal biopsy specimens. Acid-induced inhibition of gastric acid secretion was evaluated in a randomized and blinded study in which acid output was measured for 2 h during basal conditions by aspiration, for the next 2 h by intragastric titration during distention with isotonic glucose, and for the following 2 h by intragastric titration during meal stimulation with peptone. The studies were done on separate days, and intragastric pH was maintained at either 2.5 or 5.5 after administration of indomethacin or placebo. Basal acid output was not altered by indomethacin treatment. Distention of the stomach stimulated acid output significantly to a similar degree in all groups, without affecting plasma gastrin. Meal stimulation increased plasma gastrin and acid output significantly more at pH 5.5 (47 ± 12 pM, 13 ±2 mmol/30 min) than at pH 2.5 (30 ± 8 pM, 6 ± 2 mmol/30 min). No effect of indomethacin treatment was observed. It is concluded that the participation of cyclooxygenase products in the mechanisms by which acid inhibits the gastric phase of acid secretion in humans is likely to be minor. These results also cast doubt on an important physiologic role for cyclooxygenase products in the regulation of basal acid secretion or of acid secretion stimulated by distention or a peptone meal.

Effect of Peptide YY on Cephalic, Gastric, and Intestinal Phases of Gastric Acid Secretion and on the Release of Gastrointestinal Hormones

The objective of this study was to investigate the effects of a novel gut peptide, peptide YY (PYY), on the cephalic, gastric, and intestinal phases of gastric acid secretion and to explore the mechanisms involved. The cephalic phase of gastric acid secretion, stimulated by the intravenous injection of 2-deoxyglucose (75 mg/kg), was found to be inhibited by intravenous PYY (100, 200, 400 pmol/kg X h) in a dose-related fashion. Peptide YY (200 and 400 pmol/kg X h) also resulted in a significant dose-dependent inhibition of the gastric phase of acid secretion. On the other hand, PYY (400 pmol/kg X h) failed to affect the intestinal phase of gastric acid output. Serum gastrin levels were increased on infusion of 10% liver extract into stomach, but were unaffected on instillation of liver extract into duodenum. Peptide YY did not inhibit the release of gastrin in either the gastric or intestinal phase studies. Furthermore, PYY had no significant effect on either the basal release of secretin, gastric inhibitory polypeptide, pancreatic polypeptide, or neurotensin, or on the stimulated release of pancreatic polypeptide by 2-deoxyglucose. The specific binding of gastrin to its receptors on the fundic mucosa was also unaffected by PYY. These results indicate that PYY inhibits the cephalic and gastric phases of acid secretion independently, and that its actions are not mediated by either a negative effect on gastrin release or a positive effect on the release of some of the known acid inhibitors, or by an inhibition of gastrin binding to its receptors on the fundic cells. Our present findings (in combination with our previous findings of inhibition of pentagastrin- and bethanechol-stimulated gastric acid secretion by PYY, independent of the vagal cholinergic mechanism) indicate that the action of PYY is either direct on the parietal cells or is mediated by yet another, unidentified, inhibitor.

Fat Inhibits Meal-Stimulated Gastric Acid Secretion after Prostaglandin Synthesis Inhibition by Indomethacin in Man

The effect of cyclooxygenase inhibition by indomethacin on the mechanism by which fat inhibits gastric acid secretion was studied in eight healthy men. Oral 200-mg doses of indomethacin administered 15 h and 2 h before testing is known to inhibit prostaglandin synthesis by 90%, as determined by prostaglandin E2 generation assay on endoscopically obtained gastric mucosal biopsy specimens. Fat-induced inhibition of gastric acid secretion was evaluated by intragastric administration of 200 ml vegetable oil or glucose (control) for 30 min, followed by intragastric titration with peptone at pH 5.5 for 2 h. The mean acid output was significantly lower after fat (8 +/- 0.2 mmol 30 min-1) as compared with control (12 +/- 0.5 mmol 30 min-1). The fat-induced inhibition was unaffected by indomethacin treatment, and the plasma gastrin responses were similar in all groups. It is concluded that the participation of cyclooxygenase products such as prostaglandins in the mechanisms by which fat inhibits the gastric phase of acid secretion in man is likely to be minor.