Increased jejunal prostaglandin E2 concentrations in patients with acute cholera.
Supraphysiologic doses of prostaglandins (PGs) mimic the effect of cholera toxin and cAMP in the small intestine, but not all observations are explicable in terms of the theory that links PGs to cAMP. Because no data exist on endogenous PGs in human cholera we measured PGE2 concentrations in jejunal fluids and fasting intestinal flow rates of PGE2 during slow marker perfusion of proximal jejunum in nine patients with high purging cholera. Nine patients in the recovery phase of cholera or other watery diarrhoeas served as controls. In acute cholera PGE2 concentrations were significantly (p less than 0.001) raised (172-1435 (n = 9) vs 60-270 (n = 9) pg/ml) and negatively correlated (r = 0.71; p less than 0.05) to the time following onset of diarrhoea. Also fasting jejunal flow rates of PGE2 were significantly (p less than 0.005) increased (0.77-8.22 (n = 7) vs 0.21-0.92 (n = 6) ng/min), and positively correlated (r = 0.84; p less than 0.01) to stool output (2.9-9.5 ml/min). By extrapolation, at normal stool output fasting jejunal flow rates of PGE2 equalled those measured during convalescence. The results support the notion that PGs, in addition to cAMP, may play a pathophysiologic role in human cholera. As the ratio between the medians of the highest values measured during the acute phase of cholera and in late convalescence was at least 15, local intestinal PGE2 formation in full blown cholera should result in mucosal PGE2 concentrations above those required for a maximal secretory response. This observation might explain why conventional doses of aspirin and indomethacin had no significant antidiarrhoeal effect in clinical trials.
D000208:Acute Disease; D000328:Adult; D002771:Cholera / Q000378:metabolism* / Q000503:physiopathology; D015232:Dinoprostone; D006801:Humans; D007419:Intestinal Secretions / Q000378:metabolism; D007583:Jejunum / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D011458:Prostaglandins E / Q000378:metabolism*
D011458:Prostaglandins E; D015232:Dinoprostone