(2012 ) Identification of beer bitter acids regulating mechanisms of gastric acid secretion . (1975 ) Gastric acid secretion and lower-esophageal-sphincter pressure in response to coffee and caffeine . As TAS2R10 was highly expressed in parietal cells, as detected by immunohistological staining, we focused on the cellular mechanisms in HGT-1 cells, which exhibit the characteristics of parietal cells (28, 29). Nevertheless, we cannot exclude that other cell types or gastrointestinal hormones may have contributed to the detected effects in the human intervention study.
To evaluate the effect of endogenous H 2 S on distention-induced gastric acid secretion, animals in PAG-treated group received cystathionine-Î³-lyase inhibitor, propargylglycine (PAG), at 50â€‰mg/kg, i.v. concomitant with the gastric distention.
The ECL cells responded to gastrin, sulphated cholecystokinin-8 and to high K+ and Ca2+ with the parallel secretion of histamine and pancreastatin. Glycine-extended gastrin was without effect. Forskolin, an activator of adenylate cyclase, induced secretion, whereas isobutylmethylxanthine, a phosphodiesterase inhibitor, raised the basal release without enhancing the gastrin-evoked stimulation. Maximum stimulation with gastrin resulted in the release of 30% of the secretory products.
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.
All are competitive inhibitors of the histamine H 2 -receptor on parietal cells. Their duration of action mirrors their plasma elimination half-lives, and is measured in a few hours. Large doses can produce marked inhibition of basal or stimulated acid secretion, although the effect disappears quickly. This is true whether the acid secretion is stimulated physiologically by eating (mediated by gastrin and cholinergic pathways), or the sight, smell or taste of food (vagal pathways, gastrin); or experimentally by infusion of histamine, gastrin or acetylcholine. The main messages that tell the stomach to secrete acid after a meal are the release of gastrin and acetylcholine.
cells exhibited an expansion of the secretory canaliculi and appeared to be secreting acid at high rates (14). Thus, NHE2 is essential for parietal cell survival but does not appear to be directly involved in gastric acid secretion. Safe and effective inhibition of gastric acid secretion has been a long-desired goal of clinicians who treat acid-related diseases such as gastro-oesophageal reflux disease and peptic ulcer. Nowadays, two classes of drug – the histamine H 2 -receptor antagonists and the proton pump inhibitors (PPI) – achieve this goal with a high level of success.
Shifting Bacterial Communities in the Stomach May Influence Cancer Risk
In HGT-1 cells, various bitter compounds as well as caffeine stimulated proton secretion, whereby the caffeine-evoked effect was (i) shown to depend on one of its cognate receptor, TAS2R43, and adenylyl cyclase; and (ii) reduced by homoeriodictyol (HED), a known inhibitor of caffeineâ€™s bitter taste. This inhibitory effect of HED on caffeine-induced GAS was verified in healthy human subjects. These findings (i) demonstrate that bitter taste receptors in the stomach and the oral cavity are involved in the regulation of GAS and (ii) suggest that bitter tastants and bitter-masking compounds could be potentially useful therapeutics to regulate gastric pH. The findings of the present study suggest that NO produced endogenously in the human oxyntic mucosa can reduce the stimulatory effects of histamine or db-cAMP on gastric acid secretion. We obtained uniform results for gastric glands isolated from different healthy human subjects, which implies that NO released from specific cells within the secretory mucosa plays an important physiological role in the regulation of gastric acid secretion.
The intensity of this inhibition probably depends on the number of eNOS-containing endocrine-like cells that are present in the vicinity of the parietal cells. What is the physiologic role of endogenous H 2 S in regulation of gastric acid secretion?.
For instance, studies in vitro have shown that NO stimulates secretion of gastric acid in the mouse[17, 18] and bullfrog. In addition, similar results have been obtained in dogs . However, other investigations have shown that NO inhibits gastric acid secretion in the rat [13, 14], in gastric glands isolated from rabbits , and in mucosa from toads . Studies of humans have provided data indicating that NO can both inhibit and augment intragastric pH [20, 21], but it is not yet known how this compound participates in gastric acid secretion in humans.
The dual delayed-release PPI dexlansoprazole seems to respond for some of the limitations other PPIs have. discussed below, the data suggest that a more important factor may be impaired development of parietal cells. mechanisms must also maintain the appropriate electrical and ionic driving forces that are required for acid secretion. gastric mucosa (Table II), consistent with the possibility that both exchangers contribute to the maintenance of parietal cell volume.
Pharmacological agents, such as histamine H(2) receptor antagonists and acid pump inhibitors, are now the most frequently used treatment for such acid-related diseases as gastroduodenal ulcers and reflux esophagitis. Based on increased understanding of the precise mechanisms of gastric acid secretion at the level of receptors, enzymes, and cytoplasmic signal transduction systems, further possibilities exist for the development of effective antisecretory pharmacotherapy.
One group of animals received PAG at 50â€‰mg/kg, i.v. + SNP (a NO donor at 6â€‰mg/kg intragastrically)  concomitant with the gastric distention. At the end of experiment, animals were killed by cardiac exsanguination.
Fig. 1Two cell types in the mucosa of the corpus of stomach are principally responsible for secretion of acid.
Ample data from clinical trials and observational experience have confirmed the utility of these agents in the treatment of acid peptic diseases, with differential efficacy and safety characteristics between and within drug classes. Paradigms in their speed and duration of action have underscored the need for new chemical entities that, from a single dose, would provide reliable duration of acid control, particularly at night.