vasoactive-intestinal-peptide and nufenoxole

To elucidate the possible mechanism whereby nufenoxole exerts its anti-diarrheal activity, its effects on human colonic prostanoid synthesis and on Na-K-ATPase and adenylate cyclase activity were determined. Colonic Na-K-ATPase activity was significantly different in the absence and presence of nufenoxole (50 ng/ml), 1.73 +/- 0.18 and 0.99 +/- 0.17 (x +/- S.E.; N = 18) mumol Pi/mg protein per h respectively. Nufenoxole (50-800 ng/ml) did not affect basal NaF-, VIP- or PGE2-stimulated colonic adenylate cyclase activity. 6-keto PGF1 alpha and TXB2 synthesis by cultured colonic mucosa was also not affected by nufenoxole (50-800 ng/ml). Nufenoxole (800 ng/ml) induced slight inhibition of PGE2 synthesis by cultured colonic mucosa. The results obtained do not suggest that the anti-diarrheal effects of nufenoxole are related to its in vitro effects on colonic prostanoid synthesis or adenylate cyclase activity. Inhibition of colonic Na-K-ATPase activity by nufenoxole also does not explain its anti-diarrheal effects. Further studies on nufenoxole effects on the respective jejunal enzyme systems and in human subjects treated with the drug may reveal its mechanism of action.

Topics: 6-Ketoprostaglandin F1 alpha; Adenosine Triphosphatases; Adenylyl Cyclases; Ca(2+) Mg(2+)-ATPase; Colon; Dinoprostone; Enzyme Activation; Guanosine Triphosphate; Humans; In Vitro Techniques; Oxadiazoles; Prostaglandins; Prostaglandins E; Sodium Fluoride; Sodium-Potassium-Exchanging ATPase; Thromboxane B2; Vasoactive Intestinal Peptide