Effect of indomethacin on cholera-induced fluid movement, unidirectional sodium fluxes, and intestinal cAMP.
Cholera enterotoxin (CT) produces intestinal secretion associated with an elevation of intestinal cyclic AMP (cAMP). Indomethacin, a potent inhibitor of prostaglandin (PG) synthesis, decreases CT-induced secretion, although a role for PG in this process has not been demonstrated. The purpose of this study was to measure the effects of indomethacin on net fluid movement and unidirectional Na fluxes in rabbit jejunal loops exposed to CT and to correlate these findings with intestinal cAMP levels. In untreated animals (no indomethacin), CT loops secreted 0.37 ml per cm per 4 hr compared to absorption in control loops of 0.23 ml per cm per 4 hr (P less than 0.001). In indomethacin-treated animals, there was a striking reduction of secretion in CT loops (0.07 ml per cm per 4 hr, P less than 0.001). Absorption in control loops in indomethacin animals was greater than in untreated animals (0.42 ml per cm per 4 hr, P less than 0.02). Unidirectional Na fluxes were greatly depressed in indomethacin animals at 1 h in both CT and control loops. This effect disappeared by 4 hr. Intestinal cAMP levels in CT loops, although not elevated at 1 hr despite the onset of secretion, were significantly elevated at 4 hr. Indomethacin did not alter cAMP levels at 1 and 4 hr in either cholera or control loops. These studies support the view that PG synthesis is not involved in CT-induced elevation of intestinal cAMP. Indomethacin may depress intestinal secretion by inhibiting a PG-mediated step beyond the generation of cAMP or by acting on some other, as yet unidentified, biological mechanism involved in intestinal secretion.
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D000242:Cyclic AMP / Q000032:analysis*; D004768:Enterotoxins / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology*; D007408:Intestinal Absorption / Q000187:drug effects; D007419:Intestinal Secretions / Q000187:drug effects*; D007583:Jejunum / Q000032:analysis / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D011817:Rabbits; D012964:Sodium / Q000378:metabolism*; D014734:Vibrio cholerae
D004768:Enterotoxins; D012964:Sodium; D000242:Cyclic AMP; D007213:Indomethacin