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Digitaloid pregnanes promote potassium-sparing diuresis in the guinea pig.
Authors:D D Smyth  J F Templeton  V P Sashi Kumar  Y Yan  W Widajewicz  F S LaBella
Institution:Department of Pharmacology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Abstract:The synthesis of 17 alpha-acetoxy-3 beta-(beta-D-glucopyranosyl)oxy]- 6 alpha-methylpregn-4-en-20-one, the glucoside of medroxyprogesterone acetate (MPA-glu), is described. MPA-glu and 14-amino-20 beta-hydroxy-3 beta-(alpha-L-rhamnopyranosyl)oxy]-5 beta, 14 beta-pregnane (LND 623), pregnane glycosides that bind to the digitalis receptor, and digoxin, a cardiac glycoside, were infused intravenously into the anesthetized guinea pig. Each of the three steroids significantly enhanced urinary volume and sodium excretion without affecting blood pressure and creatinine clearance. Potassium excretion was markedly enhanced by digoxin but unaffected by MPA-glu or LND 623. These observations conform to previous work that demonstrated, in the rat, potassium-sparing diuresis by the glucoside of 14 beta-hydroxyprogesterone, a cardiotonic pregnane. There is a dissociation between potency to inhibit 3H]ouabain binding and the extra ATPase actions of the digitaloid pregnanes.
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