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The treatment and prevention of acid-related disorders are accomplished by decreasing gastric acidity and enhancing mucosal defense. The appreciation that an infectious agent, Helicobacter pylori, plays a key role in the pathogenesis of acid-peptic diseases has stimulated new approaches to prevention and therapy.
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PHYSIOLOGY OF GASTRIC SECRETION
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Gastric acid secretion is a complex and continuous process: neuronal (acetylcholine, ACh), paracrine (histamine), and endocrine (gastrin) factors all regulate the secretion of H+ by parietal cells (Figure 45–1).
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Specific receptors (M3, H2, and CCK2, respectively) are on the basolateral membrane of parietal cells in the body and fundus of the stomach. Some of these receptors are also present on enterochromaffin-like (ECL) cells, where they regulate the release of histamine. The H2 receptor is a GPCR that activates the Gs–adenylyl cyclase–cyclic AMP–PKA pathway. ACh and gastrin signal through GPCRs that couple to the Gq–PLC-IP3–Ca2+ pathway in parietal cells. In parietal cells, the cyclic AMP and the Ca2+-dependent pathways activate H+, K+-ATPase (the proton pump), which exchanges H+ and K+ across the parietal cell membrane. This pump generates the largest ion gradient known in vertebrates, with an intracellular pH of ~7.3 and an intracanalicular pH of ~0.8.
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ACh release from postganglionic vagal fibers directly stimulates gastric acid secretion through muscarinic M3 receptors on the basolateral membrane of parietal cells. The CNS predominantly modulates the activity of the enteric nervous system via ACh, stimulating gastric acid secretion in response to the sight, smell, taste, or anticipation of food (the "cephalic" phase of acid secretion). ACh also indirectly affects parietal cells by increasing the release of histamine from the ECL cells and of gastrin from G ...