Parietal cells gastric acid production

Gastric secretion. Stimulation of gastric acid production by vagal impulses involves an M-cholinoceptor subtype (M -receptor), probably associated with enterochromaffin cells. Pirenzepine (p. 106) displays a preferential affinity for this receptor subtype. Remarkably, the HCl-secreting parietal cells possess only Ma-receptors. Mi-receptors have also been demonstrated in the brain however, these cannot be reached by pirenzepine because its lipophilicity is too low to permit penetration of the blood-brain barrier. Pirenzepine was formerly used in the treatment of gastric and duodenal ulcers (p. 166). 

Mecfianism of Action A benzimidazole that is converted to active metabolites that irreversibly bind to and inhibit hydrogen-potassium adenosine triphosphatase, an enzyme on the surface of gastric parietal cells. Inhibits hydrogen ion transport into gastric lumen. Therapeutic Effect Increases gastric pH, reduces gastric acid production. Pharmacokinetics ... 

Lindberg et al. [169] proposed a mechanism of action for omeprazole, the inhibitor of the gastric H+/K+-ATPase, which is responsible for the gastric acid production and located in the secretory membranes of the parietal cell. Omeprazole itself is not an active inhibitor of this enzyme,... 

Gastric acid production is regulated by both the autonomic nervous system and several hormones. The parasympathetic nervous system, via the vagus nerve and the hormone gastrin, stimulates the parietal cell to produce gastric acid, acting both directly on parietal cells and indirectly through the stimulation of the secretion of the hormone histamine from ECL cells. Vasoactive intestinal peptides, cholecystokinin and secretin all inhibit acid production. 

As discussed earlier, carbonic acid is a source of protons in gastric acid (HCl) production. The bicarbonate anion, which might be considered a byproduct of gastric acid production, is transported out of the parietal cell into the bloodstream. 

Comparison of the structures of histamine with cimetidine and ranitidine. The latter two are H2-receptor antagonists and act on the gastric parietal cells to inhibit gastric acid production. Ranitidine, which has a furan rather than an imidazole structure, is a more potent competitive inhibitor than cimetidine. 

Omeprazole effectively inhibits gastric secretion by inhibiting the gastric H+, K+-ATPase. " This enzyme is responsible for gastric acid production and is located in the secretory membranes of parietal cells. Thus, omeprazole is proposed as an anti-ulcerative drug, specially in the treatment of Zollinger-Ellison syndrome. " ... 

Systemic alkalosis caused by an excessive decrease in gastric acid production is unlikely, because the drug must be activated by an acid environment within the parietal cell. Thus, the conversion of the drug to the active form is related to the amount of carbonic acid available. 

The PPIs are prodrugs, activated by exposure to pHs less than five. Once activated, the drugs bind irreversibly to the H, K+- ATPase (the proton pump ) in the parietal cell apical membrane, inhibiting its activity and decreasing gastric acid production by more than 95 %. 

Gastric juice is the product of several cell types. The parietal cells produce hydrochloric acid, chief cells release pepsinogen, and accessory cells form a mucin-containing mucus. 

C. Histamine stimulates gastric acid secretion through an effect on Hj-receptors of gastric parietal cells. Although certain antihistamines are metabolized by cytochrome P450 enzymes, histamine does not induce their production. Histamine helps to maintain a wakeful state through an effect on Hj-receptors. Histamine-mediated hronchoconstriction is mediated by Hj-receptors, while histamine-mediated vasodilation occurs as a result of stimulation of Hi- and Hj-receptors. 

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. 

Histamine has long been recognized as a powerful stimulant of gastric acid secretion and, to a lesser extent, of gastric pepsin and intrinsic factor production. The effect is caused by activation of H2 receptors on gastric parietal cells and is associated with increased adenylyl... 

Q13 Ranitidine is an example of an antagonist at histamine receptors on the parietal cells and has been in use for some years in the treatment of peptic ulceration. It blocks the H2 receptor on these acid-secreting cells, so reducing or preventing the activation of the H+-K+ ATPase proton pump and the production of HC1. It can heal both gastric and duodenal ulcers. 

Figure 4.2 Gastric add production. Two cell types in the mucosa of the corpus of stomach are principally responsible for secretion of acid. Histamine secreted from nearby enterochromaffin-like (ECL) cells stimulates parietal cells to secrete acid. A variety of substances can stimulate the ECL cell to secrete histamine, including PCAP, pituitary adenyl cyclase-activab ng peptide (released from enteric nervous system interneurones in the gastric mucosa), and gastrin, both stimulating ECL cells via adenyl cyclase to raise intracellular levels of cAMP that lead to histamine secretion.

Vitamin B] deficiency is commonly caused by pernicious anemia (PA). TA is an autoimmune disease resulting from the body s production of antibodies that recognize inlrinsic factor or other proteins of the parietal cell. The binding of antibodies to these proteins results in loss of their function. The parietal cells may be destroyed and be undetectable in patients with PA. The major defect in PA is gastric atrophy. 1 here may be a lack of all gastric secretions, including intrinsic factor, gastric acid, and pepsin. 

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