Effect of nufenoxole on human colonic prostanoid synthesis, Na-K-ATPase and adenylate cyclase activities.
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.
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism*; D017301:Ca(2+) Mg(2+)-ATPase; D003106:Colon / Q000201:enzymology* / Q000378:metabolism; D015232:Dinoprostone; D004789:Enzyme Activation / Q000187:drug effects; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D010069:Oxadiazoles / Q000494:pharmacology*; D011453:Prostaglandins / Q000096:biosynthesis*; D011458:Prostaglandins E / Q000096:biosynthesis / Q000494:pharmacology; D012969:Sodium Fluoride / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013929:Thromboxane B2 / Q000096:biosynthesis; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D010069:Oxadiazoles; D011453:Prostaglandins; D011458:Prostaglandins E; D014660:Vasoactive Intestinal Peptide; C015627:nufenoxole; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D006160:Guanosine Triphosphate; D012969:Sodium Fluoride; D000251:Adenosine Triphosphatases; D017301:Ca(2+) Mg(2+)-ATPase; D000262:Adenylyl Cyclases; D000254:Sodium-Potassium-Exchanging ATPase; D015232:Dinoprostone