Gastric acid secretion mechanism

Figure 3.1 A schematic representation of the control mechanism that stimulates gastric acid secretion, and the intervention points used to treat ulcers. The parietal cells and gastric cells form part of the epithelial cell lining of the stomach. Histamine release is usually triggered as part ofthe enteric nervous system response to distension of the stomach when food is eaten.

The search for specific inhibitors of gastric H,K-ATPase has a dual purpose. First, with the help of suitable inhibitors it is possible to get insight into the molecular mechanisms of H,K-ATPase, and second, a specific inhibitor might be clinically useful for inhibition of gastric acid secretion in anti-ulcer therapy. 

Mechanism of Action A proton pump inhibitor that selectively Inhibits the parietal cell membrane enzyme system (hydrogen-potassium adenosine triphosphatase) or proton pump. Therapeutic Effect Suppresses gastric acid secretion. Pharmacokinetics ... 

Mechanism of Action A prostaglandin that inhibits basal, nocturnal gastric acid secretion via direct action on parietal cells. Therapeutic Effect Increases production of protective gastric mucus. 

Mechanism of Action An Hj blocker and gastric acid secretion inhibitor that inhibits histamine action at histamine-2 receptors of parietal cells TherapeuticEffeet Inhibits basal and nocturnal gastric acid secretion. 

Mechanism of Action An Hj-blocker that inhibits histamine action at histaminej receptors of gastric parietal cells. Therapeutic Effect Inhibits gastric acid secretion when fasting, at night, or when stimulated by food, caffeine, or insulin. Reduces volume and hydrogen ion concentration of gastric juice. 

P. Lindberg, P. Norberg, T. Ahninger, A. Brandstram, B. Wallmark (1986). The mechanism of action of the gastric acid secretion inhibitor omeprazole. J. Med. Chem. 29 1327-1329. 

INTRODUCTION Mechanism of gastric acid secretion Inhibition of gastric acid secretion Therapeutic value of gastric acid inhibition... 

It has recently been suggested that stimulation of gastric acid secretion across the apical membrane of the gastric parietal cell predominantly reflects the insertion of an active potassium and chloride transporter/ channel rather than direct activation of HVK -ATPase. However, the mechanisms involved in and Cl transport into the gastric parietal cell are still controversial. The presence of a Cl channel in the apical membrane has been confirmed by using established d channel blockers. In vitro in rabbit isolated gastric parietal cells, 9-anthracene carboxylate and the more potent diphenylamine-2-carboxylate inhibit gastric acid formation concen-tration-dependently irrespective of the kind of stimulation [181]. Thus Cl channel blockers can be defined as indirect HVK -ATPase inhibitors. 

Gastric acid secretion can be inhibited by several mechanisms including acid in the stomach (pH 3 inhibits gastrin release), acid in the duodenum, the presence of fat in the pancreas, and hypertonic fluids or hyperglycemia. Somatostatin, a hormone produced by antral mucosal endocrine cells (D cells), inhibits the release of gastrin by directly inhibiting the parietal cells. Somatostatin is also present in other GI tissue and the pancreas. C cells, endocrine cells in the proximal small intestine, secrete secretin in response to mucosal acidification, which also decreases gastric secretion. 

The aim of this review is to outline the drugs that are currently available and the medicinal chemistry that led to their discovery. The physiological processes associated with acid secretion and the mechanism of action of inhibitors of this process are described. Current research into inhibitors of gastric acid secretion is aimed at producing a reversible PPI or antagonist of receptor-mediated acid secretion. The medicinal chemistry and pharmacology of such approaches are considered. 

---