Parietal cells acid secretion

Q3 The cells which produce HC1 are the parietal cells acid secretion can produce a stomach pH of 1.5-2. H+ is secreted into the stomach lumen by an ATP-dependent proton pump in exchange for K+. H+ secretion depends on the dissociation of carbonic acid, formed by the hydrolysis of C02, in a reaction catalysed by carbonic anhydrase ... 

Omeprazole [om ME pary zol] is the first of a new class of drugs that binds to the H7K+-ATPase enzyme system (proton pump) of the parietal cell, suppressing secretion of hydrogen ions into the gastric lumen. The membrane-bound proton pump is the final step in the secretion of gastric acid (see Figure 24.3). A second proton pump inhibitor, lansoprazole [Ian SOP ra zol], is also available. 

Q14 Proton pump inhibitors, for example omeprazole, greatly reduce secretion of gastric acid by a direct inhibitory action on the proton pumps of the parietal cells, which secrete H+ into the stomach lumen. They are used alone or in combination with the eradication of H. pylori, generally for treatment of severe reflux disease. 

Parietal cells also secrete intrinsic factor, which is necessary for the absorption of vitamin B12. Vitamin B12 is a cofactor of enzymes which synthesise tetrahydrofolic acid, which in turn is needed for the synthesis of DNA components. An impairment of DNA synthesis will affect rapidly dividing cell populations, among them the haematopoietic cells of the bone marrow, which may result in pernicious anaemia. This condition may result from a destruction of the gastric mucosa by, for example, autoimmune gastritis or the resection of large parts of the lower ileum, which is the main site of vitamin B12 absorption, or of the stomach. 

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.

ECL-cell to trigger the release of HA from storage granules located in ECL-like cells. HA, by activation of the Hg-receptor and subsequent elevation of cAMP levels, stimulates the parietal cells to secrete acid. 

After the stomach s acidic environment facilitates the breakdown of vitamin B12 bound to food, the vitamin B12 binds to the intrinsic factor released by the stomach s parietal cells. The secretion of intrinsic factor generally corresponds to the release of hydrochloric acid and serves as a cell-directed carrier protein similar to transferrin for iron. This complex, resistant to degradation, forms in the duodenum and allows for subsequent absorption of vitamin B12 in the terminal ileum. The cobalamin-intrinsic factor complex is taken up into the ileal mucosal cell, the intrinsic factor is discarded, and the cobalamin is transferred to transcobalamin It, which serves as a transport protein. This complex is secreted into the circulation and is taken up by the fiver, bone marrow, and other cells. Transcobalamin 11 has a short half-fife of 1 hour and is rapidly cleared from the blood. Consequently, most circulating cobalamin is bound to serum haptocorrins (formerly transcobalamin I and transcobalamin IB) whose function is unknown. However, it should be noted that an alternate pathway for vitamin B12 absorption independent of intrinsic factor or an intact ter-... 

Gastric secretion is under the control of hormonal, neuronal, and calcium-sensing receptors, resulting in causing the parietal cells to secrete concentrated acid with pH close to 1. A variety of in vitro and in vivo techniques have been used to study gastric secretion, with emphasis on acid secretion, in isolated parietal cells, isolated whole stomach preparation, or the use of recent technology of noninvasive in vivo telemetry methods. 

Pharmacological studies on acid secretion can be performed on mucosal cell preparation from stomach mucosa obtained by enzyme dispersion and separated by centrifugation to separate parietal cells (H" secreting cells) and histamine secreting cells, ECL cells (Brenna and Waldum 1991). 

Whereas the introduction of the Hz receptor antagonist class of agents revolutionized the management of acid peptic-related disease, it became apparent that further improvement in the regulation of the acid-secretory process would yield better clinical results. This was especially true of erosive esophagitis. The identification of the proton pump as the final step in the pathway of parietal cell add secretion provided a unique opportunity for better control of parietal cell secretion. Also, it was realized that without continuous treatment, peptic ulcer disease returned after healing the ulcer. 

The histamine H2-receptor (359 amino acids) is best known for its effect on gastric acid secretion. Histamine H2-receptor activation, in conjunction with gastrin and acetylcholine from the vagus, potently stimulate acid secretion from parietal cells. High concentrations of histamine are also present in cardiac tissues and can stimulate positive chronotropic and inotropic effects via H2-receptor stimulation and activation of adenylyl... 

The first compound of this class with inhibitory activity on the enzyme and on acid secretion was the 2-(pyridylmethyl)sulfinylbenzimidazole, timopra-zole, and the fust pump inhibitor used clinically was omeprazole, 2-[[3,5-dimethyl-4-methoxypyridin-2-yl] methylsulfinyl]-5-methoxy- lH-benzimidazole. Omeprazole is an acid-activated prodrug. Omeprazole and the other PPIs are accumulated in the acidic space of the parietal cell due to the pKa of the pyridine nitrogen and these are converted due to protonation of the benzimidazole nitrogen first to a thiol-reactive cationic sulfenic acid and then dehydrated to form the sulfenamide (Fig. 1). These thiophilic cations then bind to luminally... 

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.

Pernicious anemia arises when vitamin B,2 deficiency blocks the metabohsm of folic acid, leading to functional folate deficiency. This impairs erythropoiesis, causing immature precursors of erythrocytes to be released into the circulation (megaloblastic anemia). The commonest cause of pernicious anemia is failure of the absorption of vitamin B,2 rather than dietary deficiency. This can be due to failure of intrinsic factor secretion caused by autoimmune disease of parietal cells or to generation of anti-intrinsic factor antibodies. 

The histamine2-receptor antagonists or H2RAs (cimetidine, famotidine, nizatidine, and ranitidine) and proton pump inhibitors (omeprazole, esomeprazole, lansoprazole, pantopra-zole, and rabeprazole) reduce the amount of acid secreted into the stomach by gastric parietal cells. These agents are also helpful for nausea and vomiting related to gastric acid secretion. 

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