Studies on the mechanism of Escherichia coli heat-stable enterotoxin-induced diarrhoea in mice.
The unidirectional fluxes of Na+, Cl- and Ca2+ and activities of calmodulin in the intestinal microvillar core were studied in Escherichia coli heat-stable enterotoxin-treated mice. There was net secretion of Na+ and Cl- in toxin-treated animals, while in control animals there was net absorption of these ions. In both control and experimental animals, there was net absorption of Ca2+; however, the absorption was significantly higher (P less than 0.01) in experimental animals when compared to controls. In the presence of Ca2+-ionophore, there was a net secretion of Na+ and Cl- in controls, while the Ca2+-ionophore could not cause any change in the fluxes of these ions in experimental animals. The activity of calmodulin was significantly higher (P less than 0.01) in experimental animals. Verapamil, a calcium channel blocker, and trifluoperazine, a calmodulin inhibitor, reversed the effects of Ca2+-ionophore and heat-stable enterotoxin. These studies demonstrate that the toxin acts through Ca2+-calmodulin, and secretion of Na+ and Cl- in experimental animals is due to an increase in calcium absorption and an increase in calmodulin activity in the intestinal microvillar core.
D000818:Animals; D001427:Bacterial Toxins / Q000633:toxicity*; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism; D003967:Diarrhea / Q000139:chemically induced* / Q000378:metabolism; D004768:Enterotoxins / Q000633:toxicity*; D004926:Escherichia coli; D029968:Escherichia coli Proteins; D007408:Intestinal Absorption / Q000187:drug effects; D007413:Intestinal Mucosa / Q000187:drug effects; D051379:Mice; D012964:Sodium / Q000378:metabolism; D014268:Trifluoperazine / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D001427:Bacterial Toxins; D002147:Calmodulin; D002712:Chlorides; D004768:Enterotoxins; D029968:Escherichia coli Proteins; C034151:heat stable toxin (E coli); D014268:Trifluoperazine; D000001:Calcimycin; D012964:Sodium; D014700:Verapamil; D002118:Calcium