Gastrointestinal cytoprotection by prostaglandins.

Abstract

Progress report Gastrointestinal cytoprotection by prostaglandinsProstaglandins (PGs) are widely distributed throughout the gastrointestinal tract and affect a variety of gastrointestinal functions.The observation that PGs of the E and A series are potent inhibitors of gastric acid secretion and that PGs, especially the E compounds, are released into the gastric lumen during vagal or gastrin stimulation suggests a possible physiological role for these agents as negative feedback inhibitors of gastric secretion'-8.Further, Robert's finding that prostaglandins prevent experimental ulceration from numerous causes in different laboratory animals implies a therapeutic use of PGs as anti-ulcer drugs apart from their antisecretory effects9-".This ability of PGs to protect the cells of the gastrointestinal epithelium against a variety of potentially noxious agents which otherwise have the capability of producing cellular damage and necrosis is termed 'cytoprotection'"0-12 and has been observed with all PGs tested, whether or not they possess gastric antisecretory properties.Furthermore, the dose of PG needed for cyto- protection has been shown to be much less than the antisecretory dose for several PGs possessing this latter property.These findings suggest that the cytoprotective action of PGs may be more fundamental than other gastrointestinal actions.If this is true, the potential clinical implications of cytoprotection are far-reaching.Are prostaglandins indeed cytoprotective ?Available evidence suggests that they are.The purpose of this discussion is to review the evidence, examine possible mechanisms for this proposed cytoprotective action of PGs, and suggest clinical situations in which such protection might prove beneficial.Other gastrointestinal actions of PGs, reviewed extensively elsewhere,1012-14 will be discussed only as they relate to cytoprotection. Evidence for cytoprotection INTESTINAL PROTECTIONIn recent years a number of nonsteroidal drugs with anti-inflammatory properties have found increasing use in the treatment of clinical disorders ranging from headache to severe arthritis.Among these drugs are such medications as indomethacin and ibuprofen which share the pharmacological properties of the older drugs, aspirin and phenylbutazone.A small but consistent percentage of patients receiving these agents develop gastrointestinal intolerance which may be manifest merely as nausea and upper abdominal discomfort or result in gastritis, duodenitis, or frank ulcerations associated with bleeding15-17.This intolerance to nonsteroidal anti-inflammatory compounds (NOSAC) occurs not only in man but also in a variety of animals in which frank 75 on July 28, 2023 by guest.