Increased jejunal prostaglandin E2 concentrations in patients with acute cholera.

P Speelman, G H Rabbani, K Bukhave, J Rask-Madsen

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.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Qadri, F, Bhuiyan, T R, Dutta, K K, Raqib, R, Alam, M S, Alam, N H, Svennerholm, A-M, Mathan, M M (2004). Acute dehydrating disease caused by Vibrio cholerae serogroups O1 and O139 induce increases in innate cells and inflammatory mediators at the mucosal surface of the gut. Gut 53: 62-69 [Abstract] [Full Text]  
• Qadri, F., Raqib, R., Ahmed, F., Rahman, T., Wenneras, C., Kumar Das, S., Alam, N. H., Mathan, M. M., Svennerholm, A.-M. (2002). Increased Levels of Inflammatory Mediators in Children and Adults Infected with Vibrio cholerae O1 and O139. CVI 9: 221-229 [Abstract] [Full Text]  
• Beubler, E., Schuligoi, R., Chopra, A. K., Ribardo, D. A., Peskar, B. A. (2001). Cholera Toxin Induces Prostaglandin Synthesis via Post-Transcriptional Activation of Cyclooxygenase-2 in the Rat Jejunum. J. Pharmacol. Exp. Ther. 297: 940-945 [Abstract] [Full Text]  
• Peterson, J. W., Finkelstein, R. A., Cantu, J., Gessell, D. L., Chopra, A. K. (1999). Cholera Toxin B Subunit Activates Arachidonic Acid Metabolism. Infect. Immun. 67: 794-799 [Abstract] [Full Text]  
• Peterson, J., Ochoa, L. (1989). Role of prostaglandins and cAMP in the secretory effects of cholera toxin. Science 245: 857-859 [Abstract]