Hypothesis revisited: cystic fibrosis: a disturbance of water and electrolyte movement in exocrine secretory tissue associated with altered prostaglandin (PGE2) metabolism?

An earlier hypothesis based on the results of pancreatic studies in cystic fibrosis (CF) patients without steatorrhoea suggesting that the basic defect was related to an abnormality in control of electrolyte movement, particularly the bicarbonate ion, and water in exocrine secretory tissue is reviewed in light of recent advances in knowledge of secretory mechanisms. Evidence for defective bicarbonate-chloride exchange in a variety of CF exocrine tissues other than the pancreas is cited. Recent recognition of the close relationship between bicarbonate and mucus secretion and their stimulation by prostaglandin E2 is discussed. Consideration is given to the possibility of altered metabolism of PGE2 because of abnormal handling of essential fatty acids in CF, and an attempt is made to relate such a defect to the recent confirmation of oligosaccharide side chain differences such as an increased fucose-sialic acid ratio in CF gastrointestinal mucus and other glycoproteins. It is suggested that membrane permeability to chloride, bicarbonate-chloride exchange, and movement of water through extra- and intracellular exocrine tissues depends on modifications of the carbohydrate structure of glycoproteins during secretion and that these changes are stimulated by coordination of cell messengers PGE2, calcium, and cyclic AMP. Disturbed PGE2 metabolism in CF could inhibit these changes rendering resulting secretions dry, concentrated, and readily able to block ducts or tubes.