title: Inhibition of Na+, K+-adenosinetriphosphatase by endotoxin: a possible mechanism for endotoxin-induced cholestasis.
abstract: Cholestatic jaundice is one complication of nonhepatic gram-negative bacterial infection. The endotoxin of Escherichia coli has been reported to cause cholestasis by inhibiting the bile salt-independent fraction (BSIF) of bile in the perfused rat liver. Accordingly, the effects of lipopolysaccharides (LPS) of E. coli and Salmonella enteritidis on the Na+, K+-adenosinetriphosphatase (ATPase) in canalicular-enriched plasma membranes of rate liver were examined. At 20 microgram/ml, both endotoxins inhibited this enzyme by approximately 40%. Maximal inhibition (70%-80%) occurred at concentrations of greater than or equal to 120 microgram/ml. The LPS of neither organism exerted any effect on the activity of Mg++-ATPase or 5'-nucleotidase in the same preparations. Inhibition by the E. coli LPS appeared to be noncompetitive in nature, and the calculated Ki was 45 microgram/ml. Since the Na+, K+-ATPase may be responsible for the elaboration of BSIF, inhibition of this enzyme could be the underlying mechanism for the endotoxin-induced cholestasis.
mesh_terms: D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors*; D000818:Animals; D002779:Cholestasis / Q000139:chemically induced; D004731:Endotoxins / Q000494:pharmacology*; D008297:Male; D011188:Potassium / Q000378:metabolism; D051381:Rats; D012964:Sodium / Q000378:metabolism
chemical_list: D004731:Endotoxins; D012964:Sodium; D000251:Adenosine Triphosphatases; D011188:Potassium