Parietal cells development

The most likely reason for cobalamin deficiency is pernicious anemia (failure to absorb vitamin B 2 in the absence of intrinsic factor from parietal cells). Vitamin Bjj absorption also decreases with aging and in individuals with chronic pancreatitis. Less common reasons for Bjj deficiency include a long-term completely vegetarian diet (plants don t contain vitamin Bjj) and infection with Diphyllobothrium latum, a parasite found in raw fish. Excess vitamin B,2 is stored in the body, so deficiencies develop slowly. 

Prostaglandins inhibit the secretion of protons by the parietal cells in the stomach, which is normally increased in response to food and the hormone gastrin. Consequently, inhibition of prostaglandin synthesis by aspirin or other similar drugs results in increased secretion of protons by the stomach, which can result in considerable gastric discomfort and can, if chronic, lead to the development of a peptic ulcer. Consequently, there is some conflict between the use of such inhibitors to relieve chronic pain (see below), in diseases such as arthritis, and the risk of development of ulcers. 

Bi2 are only about 2 meg, it would take about 5 years for all of the stored vitamin B12 to be exhausted and for megaloblastic anemia to develop if Bi2 absorption were stopped. Vitamin B12 in physiologic amounts is absorbed only after it complexes with intrinsic factor, a glycoprotein secreted by the parietal cells of the gastric mucosa. Intrinsic factor combines with the vitamin Bi2 that is liberated from dietary sources in the stomach and duodenum, and the intrinsic factor-vitamin Bi2 complex is subsequently absorbed in the distal ileum by a highly selective receptor-mediated transport system. Vitamin Bi2 deficiency in humans most often results from malabsorption of vitamin B12 due either to lack of intrinsic factor or to loss or malfunction of the specific absorptive mechanism in the distal ileum. Nutritional deficiency is rare but may be seen in strict vegetarians after many years without meat, eggs, or dairy products. 

Pantoprazole sodium, a substituted benzimidazole derivative, is an irreversible proton pump inhibitor, and was developed for the treatment of acid-related gastrointestinal disorders. As with other drugs of its class (e. g. omeprazol or lansoprazole), pantoprazole reduces gastric acid secretion through inhibition of the portion on the gastric parietal cell. In combination with other drugs, pantoprazole can be used for the initial treatment of H. Pylori infection [1],... 

There are currently four racemic PPIs available on the market omeprazole, lansoprazole, pantoprazole, and rabeprazole. (More recently, enantiomerically pure versions have also been studied and developed, e.g., S-omeprazole, marketed by AstraZeneca as esomeprazole see Chapter II-2.) Proton pump inhibitors share the same core structure, the substituted pyridylmethyl-sulfmyl-benzimidazole, but differ in terms of substituents on this core structure. The absolute requirements of the core structure for the activity of PPIs was not understood until it became clear that the active PPIs are derived from inactive prodrugs the prodrugs are transformed, in the acid-secreting parietal cells, by a unique cascade of chemical structural transformations leading to the active principle, a cyclic sulfenamide species. Inhibition of acid secretion in turn is then achieved by formation of covalent disulfide bonds with key cysteines of the (H+/K+)-ATPase. 

A number of methods have been developed to permit assessment of folate and vitamin B12 nutritional status and to differentiate between deficiency of the vitamins as a cause of megaloblastic anemia. Obviously, detection of antibodies to intrinsic factor or gastric parietal cells will confirm autoimmune pernicious anemia rather than nutritional deficiency of either vitamin. 

A complement-fixing antibody in the serum of pernicious anemia patients, diabetics, and those widi iron-deficiency anemia has been detected against mucosal extracts of the fundus and body of the hmnan stomach and the microsomal fraction of gastric mucosal extracts (D8, 14, M8, M48, RIO, TI3). Immunofluorescent studies have shown that activity is directed against gastric parietal cell cytoplasm (15, RIO, T13) and probably represents another type of antibody, which develops about twice as frequently as the one directed against intrinsic factor in pernicious anemia serum (Fig. 27). 

During acidosis, the cells of the renal tubule can respond by inserting two proteins into the apical region of the plasma membrane. (The apical part is that region that is exposed to the developing urine.) The two proteins are H,K-ATPase and H+-ATPase. H,K-ATPase, and the enzymes that act in concert with it, is better known as a component of the parietal cell where it creates stomach acid. The other proton pump of the renal tubule, which is H" -ATPase, is closely related to FoFiH" -ATPase of the mitochondrial membrane. Hence, anyone who imderstands how protons are pumped out of the mitochondrion and how stomach acid is made will clearly understand how the renal tubule can shuttle protons to the lumen of the renal tubule and into the developing urine. 

Scarff K L, Judd L M, Toh B H et al 1999 Gastric H(+), K(+)-adenosine triphosphatase beta subunit is required for normal function, development and membrane structure of mouse parietal cells. Gastroenterology 117 605-618... 

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