Gastroduodenal mucosal defense: role of endogenous mediators

Abstract

The remarkable resistance of the mucosal lining of the upper gastrointestinal tract to concentrated gastric acid remains one of the biggest unsolved mysteries of upper gastrointestinal physiology. In the past year, there have been prominent findings regarding prostaglandin subtypes, growth factors, proteinase-activated receptors, peroxisome proliferator-activated receptors, and nitric oxide releasing nonsteroidal antiinflammatory agents. The prostaglandin I receptor subtype is involved with the mucosal acid-sensing neural circuit termed the capsaicin pathway. Proteinase-activated receptors and peroxisome proliferator activated receptor-gamma are important components of host defense against acid injury. Nitric oxide releasing nonsteroidal antiinflammatory agents have potential usefulness in subjects with mucosal injury related to the use of nonsteroidal antiinflammatory agents and may be an important alternative to selective cyclooxygenase-2 inhibitors for patients who need aspirin cotherapy for the prevention of arterial thrombus formation. Peptic ulcer disease, although declining in prevalence, appears to be increasing in virulence, perhaps because of the overall aging of the population and improved care in the intensive care unit. Although Helicobacter pylori and nonsteroidal antiinflammatory agents have been identified as key pro-ulcerogenic factors, many ulcers may also result from a deficiency of other, unknown host protective factors. A more detailed understanding of the host factors involved in mucosal protection will thus help identify novel therapeutic targets aimed at the prevention and treatment of upper gastrointestinal tract mucosal injury.