Gastric Acid Secretion

alpha-Calcitonin gene-related peptide (alphaCGRP) is a pleiotropic peptide neuromodulator that is widely expressed throughout the Central and peripheral nervous systems. CGRP has been implicated in a variety of physiological processes including peripheral vasodilation, cardiac acceleration nicotinic acetylcholine receptor (AChR) synthesis and function, testicular descent, nociception, carbohydrate metabolism, gastrointestinal motility, neurogenic inflammation, and gastric acid secretion. To provide a better understanding of the physiological role(s) mediated by this peptide neurotransmitter, we have generated alphaCGRP-null mice by targeted modification in embryonic stem cells. Mice lacking alpha CGRP expression demonstrate no obvious phenotypic differences from their wild-type littermates. Detailed analysis of systemic cardiovascular function revealed no differences between control and mutant mice regarding heart rate and blood pressure under basal or exercise-induced conditions an...

The effects of adaptation to two diets differing in the type of dietary fat on the circulating levels of secretin, cholecystokinin, and pancreatic polypeptide, were investigated in humans. A relationship with the results concerning gastric acid secretion and gastrin release previously described by us, was also examined. The

This study examines the putative gastroprotective effect of adenosine on indomethacin-induced gastric lesions and the possible mechanisms involved. After 24 hr of starvation, the rats were treated either with indomethacin (Indo; 25 mg/kg, subcutaneously) alone or adenosine + Indo (Ado; 7.5 mg/kg, subcutaneously, three times a day), or the vehicle (5% NaHCO3, subcutaneously). The length of hemorrhagic lesions in the stomachs was expressed as the lesion index. The tissue-associated myeloperoxidase (MPO) activity and protein oxidation were measured in gastric tissue samples. Formation of reactive oxygen species in gastric tissues was measured by using luminol- and lucigenin-enhanced chemiluminescence. In other groups of rats, gastric mucosal permeability and gastric acid output were performed following the same treatment regimens. The gastric mucosal permeability was measured by determination of [51Cr]EDTA clearance in a perfused stomach preparation and gastric acid secretion studies w...

The effect of cyclic somatostatin on pentagastrin-and histamine-stimulated gastric acid secretion in conscious cats was studied. Evidence is produced that somatostatin competitively inhibits pentagastrin-stimulated gastric acid secretion whereas it inhibits histamine-stimulated secretion by a mechanism which is not competitive in nature. The vagus nerves seem to be involved in the mode of action of somatostatin as the inhibitory effects are greater in vagotomized than in vagus intact animals.

To overcome the gastric toxicity of aspirin and ketorolac fi ve different N,N-disubstitutedaminoethyl ester derivatives for each were synthesized and evaluated. The intact esters were specially designed to satisfy the structural requirement for possessing the anticholinergic activity before cleavage. Besides blocking the acidic carboxyl group by esterifi cation this activity was incorporated into the synthesized esters with an expected additional benefi t of having reduced gastric acid secretion and thereby abolishing the local irritation by a dual mechanism. This report describes the synthesis, hydrolysis kinetics and the biological activity of these esters. All the ester derivatives were found to be stable in buffers (pH 2.0 and 7.4) for suffi cient time period, assuring them to be absorbed intact and to successfully overcome the local gastric irritation of the parent drug. A fast enzymatic hydrolysis was observed for all the derivatives in 80% pooled human serum. The synthesized ...

Even though rabbit gastric glands are a commonly used model for the study of gastric physiology, little is known about the secretion of gastric acid in the rabbit in vivo. Gastric acid secretion in response to pentagastrin, histamine, and bethanechol stimulation, and the effect of specific cholinergic and histamine H2-receptor blockers was studied in 62 urethane-anesthetized rabbits. Additionally, the responses of eight conscious rabbits prepared with chronic gastric fistula were compared with similarly prepared conscious dogs (n = 10) and conscious rats (n = 18). In anesthetized rabbits, maximal pentagastrin stimulation resulted in acid outputs only 22% that of maximal histamine stimulation, but this was enhanced by restoring cholinergic tone with a subthreshold infusion of bethanechol. In conscious rabbits, pentagastrin was an effective stimulant, resulting in maximal acid output 70% that of maximal histamine stimulation. This is in contrast to the in vitro findings reported reported by others utilizing isolated gastric glands and cells. Histamine was a potent stimulant of acid secretion in both the anesthetized and conscious rabbit, an observation that parallels the in vitro findings. Unlike the dog and rat, atropine was ineffective as an inhibitor of histamine-stimulated acid secretion in the conscious rabbit, although it was marginally effective against histamine in anesthetized rabbits and against pentagastrin in conscious rabbits. It is concluded that cholinergic tone plays a crucial role in pentagastrin-stimulated acid secretion in the rabbit. This may be an explanation for the poor response to pentagastrin described in isolated rabbit gastric gland preparations.

Gastric parietal cells secrete acid into the lumen of the stomach. They express a proton pump, the gastric H(+)/K(+) ATPase, the activity of which is tightly regulated. The H(+)/K(+) ATPase traffics between an intracytoplasmic compartment (tubulovesicles) in quiescent parietal cells and the apical plasma membrane in activated cells. These trafficking events are considered to contribute to the control of acid secretion by modulating access to apical K(+) and Cl(-) conductances that are required for transmembrane H(+) ion transport by the H(+)/K(+) ATPase. Here, we have determined whether the control of acid secretion in vivo requires membrane trafficking of the H(+)/K(+) ATPase. We developed mice that only express an H(+)/K(+) ATPase beta subunit in which a putative tyrosine-based endocytosis motif in the cytoplasmic tail is mutated. Location of the H(+)/K(+) ATPase and parietal cell ultrastructure and gastric acid secretion were then examined. Parietal cells of these mice lacked a t...

SUMMARY 1. The effect of somatostatin and eighteen somatostatin analogues on penta-gastrin-stimulated gastric acid and pepsin secretion was investigated in the conscious vagotomized cat prepared with chronic gastric fistulae. The majority of the analogues are peptides where D-amino acids are incorporated into the molecule instead of the natural L-isomers. 2. The ID50 for cyclic-somatostatin inhibition of near-maximal gastric acid secretion stimulated by pentagastrin 8 jug kg-1 hr-1 was found to be 1-29 + 0-13 n-mole kg-1 hr-1. Pentagastrin-stimulated pepsin secretion had a lower threshold to somatostatin inhibition than did acid secretion. 3. D-Phe6, D-Phe7, D-Thr10, D-Thr12 and D-Phe6-D-Trp5 analogues all show low biological activity against the secretion of gastric acid and pepsin, growth hormone, insulin and glucagon. None of these analogues are antagonists of the cyclic-somato-statin inhibition of gastric secretion, suggesting that they have low affinity for this somatostatin receptor. 4. The analogues under investigation show parallel changes in activity against gastric and growth hormone secretion, suggesting a similarity between the gastric and growth hormone receptors for somatostatin. 5. D-Cys14 analogues are equipotent with or have a greater potency than cyclic-somatostatin in inhibiting the secretion of gastric acid, growth hormone and glucagon but show low insulin inhibiting activity.

SUMMARY 1. The effect of somatostatin and eighteen somatostatin analogues on penta-gastrin-stimulated gastric acid and pepsin secretion was investigated in the conscious vagotomized cat prepared with chronic gastric fistulae. The majority of the analogues are peptides where D-amino acids are incorporated into the molecule instead of the natural L-isomers. 2. The ID50 for cyclic-somatostatin inhibition of near-maximal gastric acid secretion stimulated by pentagastrin 8 jug kg-1 hr-1 was found to be 1-29 + 0-13 n-mole kg-1 hr-1. Pentagastrin-stimulated pepsin secretion had a lower threshold to somatostatin inhibition than did acid secretion. 3. D-Phe6, D-Phe7, D-Thr10, D-Thr12 and D-Phe6-D-Trp5 analogues all show low biological activity against the secretion of gastric acid and pepsin, growth hormone, insulin and glucagon. None of these analogues are antagonists of the cyclic-somato-statin inhibition of gastric secretion, suggesting that they have low affinity for this somatostatin receptor. 4. The analogues under investigation show parallel changes in activity against gastric and growth hormone secretion, suggesting a similarity between the gastric and growth hormone receptors for somatostatin. 5. D-Cys14 analogues are equipotent with or have a greater potency than cyclic-somatostatin in inhibiting the secretion of gastric acid, growth hormone and glucagon but show low insulin inhibiting activity.

Compared to the well-known anti-ulcerogenic properties of tricyclic antidepressants, the impact of selective serotonin reuptake inhibitors (SSRIs) on gastric mucosa is less clear. Human clinical trials have shown that SSRIs and non-steroidal anti-inflammatory drugs (NSAIDs) act synergistically and promote stomach ulcer formation and upper gastrointestinal tract bleeding. Acute SSRI treatment confers an additional risk for the formation of NSAID-induced gastric ulcers through increase in gastric acid secretion. Stress, which is often experienced by depressed patients, also deteriorates the gastric environment. Thus the potential for exacerbating stress-induced gastric lesions must be considered before prescribing SSRIs. Therefore, we evaluated the effects of paroxetine by using a water-immersion stress-induced stomach ulcer model of mice, by examining single vs. repeated paroxetine treatments for 8 and 22 days before stress induction. Repeated administration of paroxetine significantly decreased the area of stress-induced stomach lesions. Although stress significantly increased the serum corticosterone concentrations, the levels were not affected by the 8-day paroxetine treatment. We confirmed the anxiolytic and antidepressive effects of 8-day paroxetine treatment at 1 and 5 days after stress induction by using the elevated plus-maze and tail-suspension tests. We concluded that repeated paroxetine treatment significantly attenuates the stress-induced ulcerogenic process in the stomach.► Diminished platelet function by SSRI treatment raises the risk for gastric lesions. ► Very few studies have focused on the effects of SSRI treatment on stomach lesions. ► Eight-day paroxetine treatment significantly reduced stress-induced stomach erosion. ► We considered the protective effect is due to an induced state of stress resilience.

Acid-peptic ulcers and diseases have been increasingly on rise in today's era of globalization, which is characterized by hurry, worry, and curry. This review summarizes various disorders associated with increased gastric acid secretion and various therapeutic ...

The endogenous ligand for the growth hormone secretagogue receptor, ghrelin, is a 28–amino-acid peptide acylated with an octanoyl group at the serine in position 3. Most of the circulating ghrelin results from its synthesis and secretion by the X/A-like endocrine cells from the stomach and proximal small intestine. Besides its potent growth hormone secretory action, ghrelin is a highly pleiotropic hormone, contributing significantly to the regulation of appetite and food intake control, gastrointestinal motility, gastric acid secretion, endocrine ...