Peptic Ulcer and its Mechanisms of Action

Peptic Ulcer

It’s mainly occurs in that part of the g.i.t (gastrointestinal tract) which is exposed to gastric acid and pepsin, i.e. the stomach and duodenum. The physiology of peptic ulcer is not clearly known. It results probably due to an imbalance between the aggressive (acid, pepsin, bile and H. pylori) and the defensive (gastric mucus and bicarbonate\ secretion, prostaglandins, nitric oxide, high\ mucosal blood flow, innate resistance of the mucosal cells) factors. A variety of psychosomatic, humoral and vascular derangements have been implicated and the importance of Helicobacter pylori infection as a contributor to ulcer formation and recurrence has been recognized. In gastric ulcer, generally acid secretion is normal or low, while deficient mucosal defense (mostly impaired mucus and bicarbonate secretion) plays a greater role. In duodenal ulcer, acid secretion is high in about half of the patients but normal in the rest. Whether production of acid is normal or high, peptic ulcer does contribute to ulceration as an aggressive factor, reduction of which is the main approach to ulcer treatment. An understanding of the mechanism and control of gastric acid secretion will elucidate the targets of antisecretory drug action.

Mechanisms of Action of Peptic Ulcer

The mechanisms operating at the gastric parietal cells are summarized in The terminal enzyme H+K+ATPase (proton pump) which secretes H+ ions in the apical canaliculi of parietal cells can be activated by histamine, ACh and gastrin acting via their own receptors located on the basolateral membrane of these cells. Out of the three physiological secretagogues, histamine, acting through H2 receptors, plays the dominant role, because the other two, gastrin and ACh

act partly directly and to a greater extent indirectly by releasing histamine from paracrine enterochromaffin-like (ECL) cells called “histaminocytes” located in the oxyntic glands. While H2 receptors activate H+K+ATPase by generating cAMP, muscarinic and gastrin/cholecystokinin (CCK2) receptors appear to function through the phospholipase C → IP3–DAG pathway that mobilizes intracellular Ca2+. The cAMP and proton pump activation also involve Ca2+. Secretomotor response to gastrin and cholinergic agonists is expressed fully only in the presence of cAMP generated by H2 activation. Some of histamines are participates in the acid secretion response to gastrin and ACh at more than one levels, and H2 antagonists suppress not only histamine, but also ACh, Penta gastrin also in fact any gastric acid secretory stimulus.