Gastric mucosa resistance

Omeprazole (p. 167) can cause maximal inhibition of HCl secretion. Given orally in gastric juice-resistant capsules, it reaches parietal cells via the blood. In the acidic milieu of the mucosa, an active metabolite is formed and binds covalently to the ATP-driven proton pump (H+/K+ ATPase) that transports H+ in exchange for IC into the gastric juice. Lansoprazole and pantoprazole produce analogous effects. The proton pump inhibitors are first-line drugs for the treatment of gastroesophageal reflux disease. 

The discovery, in 1979, by Robert [123] of the remarkable ability of prostaglandins (PG) to increase the resistance of the gastric mucosa to damage started research on the role of defensive factors, such as the mucus-bicarbonate barrier, mucosal blood flow, neutralization of free radicals, stabilization of lisosomal membranes or nitric oxide on the gastric mucosal integrity. 

E. E. Crane and R. E. Davies, Electrical Potential Difference and Resistance of Isolated Frog Gastric Mucosa and Other Secretary Membranes, Trans. Faraday Soc. 46, 598 (1950). 

V.B12 is also known as antipemicious anemia factor. Pernicious anemia is characterized by a severely reduced production of red blood cells, deficient gastric secretion and disturbances of the nervous system. It is not usually caused by dietary deficiency of V.B]2, but by the absence of intrirrsic factor, which is required for V.B[2 absorption. Intrinsic factor is a neuraminic acid-containing glycoprotein, normally present in the gastric mucosa, which forms a pepsin-resistant complex with V.B,2, and enables V.B,2 absorption in the lower part of the intestinal traet. 

By 1975 Rehm s own measurements made with microelectrodes of the resistances in the gastric mucosa had convinced him that the resistance pathway linking the surface epithelial cells with the parietal cells is not low enough to be compatible with this version of the separate site hypothesis. He was left wondering what the surface cells secrete. 

Both cellular and paracellular pathways contribute to duodenal bicarbonate secretion. The paracellular pathway contributes approximately 40% of net HCO3 secretion in this tissue—a much larger fraction than in the gastric mucosa. This is due to the low resistance of the paracellular pathway in this tissue. Cellular secretion is stimulated by various agents, but there is abundant spedes variation. In humans, CCK, prostaglandins, and VIP stimulate secretion. Intracellular stimulants, such as dibutyryl cAMP (dbcAAAP) and forskolin, stimulate... 

Klinkenberg-Knol EC, Nelis F, Dent J, et al. Long-term omeprazole treatment in resistant gastroesophageal reflux disease efficacy, safety, and influence on gastric mucosa. Gastroenterology 2000 118 661 -669. 

Vitamin B12 is special in as far as its absorption depends on the availability of several secretory proteins, the most important being the so-called intrinsic factor (IF). IF is produced by the parietal cells of the fundic mucosa in man and is secreted simultaneously with HC1. In the small intestine, vitamin B12 (extrinsic factor) binds to the alkali-stable gastric glycoprotein IF. The molecules form a complex that resists intestinal proteolysis. In the ileum, the IF-vitamin B 12-complex attaches to specific mucosal receptors of the microvilli as soon as the chymus reaches a neutral pH. Then either cobalamin alone or the complex as a whole enters the mucosal cell. 

Pancreatic enemies (B) from slaughtered animals are used to relieve excretory insufficiency of the pancreas ( disrupted digestion of fats steatorrhea, inter alia). Normally, secretion of pancreatic enzymes is activated by cholecystokinin ancreozymin, the en-terohormone that is released into blood from the duodenal mucosa upon contact with chyme. With oral administration of pancreatic enzymes, allowance must be made for their partial inactivation by gastric acid (the lipases, particularly). Therefore, they are administered in acid-resistant dosage forms. 

The normal gastroduodenal mucosa has the following three defense mechanisms for resisting injury arising from the acid and peptic activity in gastric juice. 

For the chamber, see Rehm WS, Dennis WH, Schlesinger H. Electrical resistance of the mammalian stomach. Am J Physiol 181 451-470, 1955. For attempts to modify the blood, see Thull NB, Rehm WS. Composition and osmolarity of gastric juice as a function of plasma osmolarity. Am J Physiol 185 317-324,1956. For early isolated mucosa work, see Rehn WS. Acid secretion, resistance, short-circuit current and voltage clamping in frog s stomach. Am J Physiol 203 63-72, 1962. 

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