INHIBITION OF NA,K-ATPASE BY AN ENDOTOXIN EXTRACTED FROM LEPTOSPIRA-INTERROGANS - A POSSIBLE MECHANISM FOR THE PHYSIOPATHOLOGY OF LEPTOSPIROSIS

Clinical manifestations of leptospirosis include disorders of the elec trolytical balance which might be related to inhibition of Na,K-ATPase . Although the physiopathological cellular mechanism of leptospirosis remains unknown, a bacterial endotoxin has been incriminated. Therefor e, we evaluated whether a glycolipoprotein fraction extracted from Lep tospira interrogans and known to be cytotoxic might inhibit Na,K-ATPas e. This glycolipoprotein fraction (GLP) inhibited Na,K-ATPase activity in rabbit kidney epithelial cells as well as Na,K-ATPase purified fro m rabbit kidney medulla. Inhibition was dose-dependent, and at maximum it almost abolished Na,K-ATPase activity whereas it had no effect on other enzymes. The GLP did not-change the apparent affinity of Na,K-AT Pase for potassium whereas it increased that far sodium, revealing a m echanism of inhibition different from that of ouabain. Finally, the in hibitory principle present in the GLP preparation was thermostable and was curtailed by the presence of albumin. In conclusion, a glycolipop roteic fraction extracted from Leptospira interrogans contains a speci fic inhibitor of Na,K-ATPase. This glycolipoproteic fraction which is present in diseased tissues might induce, through this inhibitor cellu lar dysfunctions responsible for the symptoms, in particular those ass ociated with electrolytical disorders such as disturbances of-renal el ectrolyte handling, cardiac arrhythmia or diarrhoea.