immunohistochemical data from that investigation revealed the presence of endogenous NOS in epithelial cells of the normal human oxyntic mucosa, more precisely, in both surface mucous cells and endocrine cells. In addition, we observed that there were close contacts between eNOS-positive cells and parietal cells either because the eNOS-positive cells contacted parietal cells via cytoplasmic processes or were invaginated by a parietal cell. Based on these findings, together with the chemical properties of NO, we concluded that NO derived from the endocrine-like cells might be a paracrine regulator of gastric acid secretion. In the present study, our aim was to verify the effect of exogenous NO on histamine- and cAMP-stimulated gastric acid secretion in humans, and also to determine whether endogenously derived NO has a functional effect on human parietal cells.
Thus, the inhibitory effect of H 2 S on gastric acid secretion is partly mediated through an increase in the gene expression of eNOS and at the same time an increase in NO production/release, resulting in the inhibition of acid secretion. As shown in the present study, an intravenous injection of H 2 S donor, NaHS, and five-day pretreatment of H 2 S precursor, L-cysteine, decreased the acid output in response to gastric distention (Figures 1 and 2). The results also showed the antisecretory effect of H 2 S significantly reduced by L-NAME pretreatment.
During the gastric phase a vagal reflex initiated by distension of the stomach further increases vagus nerve stimulation. In addition, local production of food metabolites, especially proteins and amino acids, directly induce gastrin release from G Cells. This study shows that caffeine’s effect on gastric acid secretion (GAS) is more complex than has been previously thought. Oral and gastric bitter taste receptors are involved in the regulation of GAS in humans.
The three stimulants of gastric acid secretion likely to have physiological roles in regulation of secretion are acetylcholine, gastrin, and histamine. Acetylcholine is released by vagal and intramucosal reflex stimulation, acting directly on the parietal cell. Gastrin is released by peptides and free amino acids in the stomach and is the only known hormonal stimulant of acid secretion. Release of gastrin by acetylcholine may occur.
They are converted into an active form by a high acid concentration, e.g. omeprazole becomes a sulfenamide. In the gastric lumen this activation by acid is a problem.
This phase continues until the food has left the stomach. Gastrin is in the stomach and stimulates the gastric glands to secrete pepsinogen (an inactive form of the enzyme pepsin) and hydrochloric acid. The secretion of gastrin is stimulated by food arriving in the stomach.
Since OMZ was launched into the market in Europe in 1988, this new and effective approach to suppress gastric acid secretion proved to be clinically superior to the H 2 -receptor antagonists . The advent of powerful acid-suppressive drugs, such as proton pump inhibitors (PPIs), has revolutionized the management of acid-related diseases and has minimized the role of surgery. The major and universally recognized indications for their use are represented by treatment of gastro-esophageal reflux disease, eradication of Helicobacter pylori infection in combination with antibiotics, therapy of H.
They received L-cysteine (50â€‰mg/kg, i.p.) or saline once a day for 5 days before stimulation of the gastric acid secretion. To quantify the mRNA expressions of eNOS, COX-2, and H + /K + -ATPase Î±-subunit, 100â€‰mg of gastric mucosa was collected, snap-frozen, and stored in liquid nitrogen. H 2 S has been shown to increase the release of NO from vascular endothelium . Moreover, it has been reported that NaHS, a H 2 S donor, induces the duodenal release of NO in rat .
These cells also produce mucus, which forms a viscous physical barrier to prevent gastric acid from damaging the stomach. The pancreas further produces large amounts of bicarbonate and secretes bicarbonate through the pancreatic duct to the duodenum to completely neutralize any gastric acid that passes further down into the digestive tract. Parietal cells contain an extensive secretory network (called canaliculi) from which the HCl is secreted by active transport into the stomach.
Acid continues to be secreted during the gastric phase in response to distension and to the peptides and amino acids that are liberated from protein as digestion proceeds. The chemical action of free amino acids and peptides excites the liberation of gastrin from the antrum into the circulation. Thus, there are mechanical, chemical, and hormonal factors contributing to the gastric secretory response to eating.
Lansoprazole (both doses) as well as omeprazole raised the plasma gastrin levels about 11-fold 2 h after dosing and 8-to 10-fold 24 h after dosing, reflecting complete (2 h) and 70-80% (24 h) reductions of gastric acid secretion. Administration of either drug for 10 weeks increased the weight of the stomach and the oxyntic mucosa. The oxyntic mucosal histidine decarboxylase activity, histamine concentration and ECL cell density were increased to the same extent in the rats given either of the two lansoprazole doses or omeprazole.
N-ethylmaleimide inhibited the (H+ + K+)-ATPase and decreased the binding of [14C]AG-1749 to the microsomes. The inhibitory effect of AG-1749 gradually increased with incubation time, and was enhanced by lowering the pH. AG-2000 and AG-1812, acid-induced rearrangement products of AG-1749, inhibited (H+ + K+)-ATPase potently, rapidly and independently of pH; the inhibition was antagonized by dithiothreitol. We propose that AG-1749 is transformed into its active forms within the acidic compartment of the parietal cells and that the active compounds inhibit (H+ + K+)-ATPase activity by reacting with the SH groups of the enzyme. significantly higher than in the control.
Recently, there is a growing body of text that has been demonstrated by H 2 S that acts as a rescue molecule for mucosal defense. Till now the mechanisms underlying the gastroprotective effects of hydrogen sulfide were attributed to maintenance and/or elevation of gastric mucosal blood flow , stimulation of bicarbonate secretion , reduction of proinflammatory cytokine expression/release [9, 26], increase of prostaglandin synthesis , decrease of reactive oxygen metabolite production , and enhancement of tissue repair [8, 27]. The findings of the present study showed that the antisecretory effect of H 2 S could be the other possible protective mechanism. According to Figure 4, the gene expression of eNOS was significantly increased by NaHS and L-cysteine as compared with the corresponding controls.
That assumption may be supported by a number of other conditions. For example, NO can easily penetrate cell membranes, which may indicate an intracellular site of action. Also, NO has a rather short life span, which implies that sources needed to generate this oxide must be available close to the NO target cell. In this study, the occurrence of eNOS in the glands is shown, but earlier extensive investigations using antibodies against both nNOS and iNOS have not revealed presence of any of the two isoforms in the glandular epithelium of normal human subjects (unpublished observation). Similar to results obtained in a study of isolated rabbit gastric glands, we found that the NOS inhibitors L-NAME and L-NNA, but not D-NAME, amplified the secretion-stimulating effect of histamine, which further indicates that the isolated human glands we used contained the enzyme NOS.
The slope was calculated between the point when pH decreases and the point at which the original pH is reached again. First, we found that oral consumption of caffeine delayed GAS in healthy subjects, whereas caffeine that was administered encapsulated, being released in the stomach, accelerated this process compared with oral administration. The delay induced by oral caffeine presentation might be explained by findings reported by McMullen et al. (36). They demonstrated that caffeine in a coffee drink accelerated the heart rate without increasing the vascular tonus in comparison with caffeine administered encapsulated concomitantly to a decaffeinated coffee drink. The increase in heart rate was likely induced by vagal withdrawal instead of sympathetic activation.