The Role of Eicosanoids in the Gastrointestinal Tract

Abstract

Rask-Madsen. The role of eicosanoids in the gastrointestinal tract.

Exploring the role of eicosanoids in the gastrointestinal tract entails fundamental problems of methodology and interpretation. Most important are the difficulties inherent in the choice of an experimental design which prevents non-specific stimulation of eicosanoid formation, because any perturbation of cell membranes will initiate eicosanoid synthesis.

In addition to cyclic nucleotides, prostaglandins may serve as intracellular mediators for the stimulus of secretion coupling via intracelluar free calcium in the gastrointestinal epithelial cells. By contrast, the effects of supraphysiological doses of prostaglandins parallel those of cyclic AMP-dependent secretagogues such as VIP, which increases calcium through activation of the mucosal adenylatecyclase.

The question of whether patients develop gastric or duodenal ulcers as a result of a prostaglandin deficiency remains open. The synthetic prostaglandin analogues available commercially for anti-ulcer therapy appear to be unable to accelerate the healing of peptic ulcers unless they are administered in anti-secretory doses, and are unlikely to have a substantial effect on patients with bleeding from ulcerative lesions in the gastro-duodenal mucosa.

prostaglandins of the E type mediate, at least partly, the diarrhoea associated with a large number of clinical conditions and various pharmacological agents. Several types of secretory diarrhoea respond to drugs that inhibit prostaglandin biosynthesis. Whether eicosanoids are mediators, or merely epiphenomena, of inflammation in ulcerative colitis and Crohn's disease remains unclear. Improved knowledge of their functional role of eicosanoids has never theless allowed a reinterpretation of the rationale behind current therapy. Uncontrolled formation of eicosanoids may not only he the source of diarrhoea in colonic inflammation, but may also he critical for cell proliferation and the development of dysplasia in long-standing disease.

Key Words:

• Crohn's disease
• diarrhoea
• eicosanoids
• intestine
• small
• intestine
• large
• peptic ulcer
• prostaglandins
• stomach
• colitis
• ulcerative