Pharmacological control of gastric acid secretion: molecular and cellular aspects.

Chronic ulceration of the gastroduodenal mucosa is one of the most common, so called "civilization diseases" of the gastrointestinal tract in industrially developed countries. Although the primary cause of gastric and duodenal peptic ulcers is unknown, gastric acid secretion is believed to play an important role in this major pathology. Gastric peptic ulcers, which represent 20% of all peptic ulcers (472) are mostly located in the antrum adjacent to the border of the acid producing fundic mucosa. Epidemiologically, gastric cancer is not reported to be increased in gastric ulcer disease. However, gastric endocrine cell hyperplasia and gastric carcinoid tumors have been described in two naturally occurring hypergastrinemic states, gastric atrophy with achlorhydria and Zollinger~Ellison syndrome (44, 45, 64, 363,408). Many hormones, growth factors, and local bioregulators are able to influence gastric secretions and to induce the ulcerogenic cascade or to preserve the integrity of the mucosa. This paper analyses different aspects of the molecular and genetic mechanisms involved in the pathophysiology of gastric secretions. At the same time it describes the complex interconnections between the signal transduction systems implied in the regulation of the secretory activity of parietal cells, and adjacent mucosal cells. Particular reference is focused on the development of the histamine H 2 receptor antagonists and the H +, K+-ATPase inhibitors in the treatment of peptic ulcer disease.