Prostaglandin Synthesis in the Human Gastrointestinal Mucosa

Abstract

Prostaglandins derive from polyunsaturated fatty acids, of which arachidonic acid is the most abundant. Arachidonic acid occurs in all cell membranes, where it is bound to phospholipids and can, once liberated by phospholipases, be metabolized by cyclooxygenase into prostaglandins and throniboxanes and by lipoxygenases into hydroxyacids, leukotrienes and lipoxins. In most studies on prostaglandin formation in the human gastrointestinal m ucosa PGE₂ and PGF_2α seem to be the regularly occurring products. Quantification of mucosal prostaglandin synthesis in vivo is problematic. Mechanical handling of tissues immediately activates arachidonic acid metabolism, and the determination of “tissue levels” of prostaglandins or prostaglandin biosynthesis in biopsy specimens ex vivo thus becomes unreliable as a measure of in vivo formation. A more reliable approach may be to measure prostaglandins in gastrointestinal luminal contents, which can be obtained atraumatically. Most measurements are made by radioimmunological methods, but the specificity of most assays has not been satisfactorily examined. More specific methods such as gas chromatography-mass spectrometry should be used to validate of a radioimmunoassays. Prostaglandin E₂, which can be measured by gas chromatography-mass spectrometry, is regularly found in human gastroduodenal luminal contents. Exposure of the mucosa to hydrochloric acid increases the output of PGE₂ to the lumen, indicating increased mucosal PGE₂ formation during physiological activation of mucosal defense mechanisms.