Digitaloid pregnanes promote potassium-sparing diuresis in the guinea pig.
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.
Smyth
D D
DD
Department of Pharmacology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Templeton
J F
JF
Sashi Kumar
V P
VP
Yan
Y
Y
Widajewicz
W
W
LaBella
F S
FS
D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology; D004231:Diuresis / Q000187:drug effects*; D005960:Glucosides / Q000138:chemical synthesis / Q000494:pharmacology*; D006168:Guinea Pigs; D007668:Kidney / Q000187:drug effects; D008297:Male; D008362:Mannosides / Q000494:pharmacology; D008525:Medroxyprogesterone / Q000494:pharmacology; D017258:Medroxyprogesterone Acetate / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D010042:Ouabain / Q000378:metabolism; D011188:Potassium / Q000378:metabolism*; D011278:Pregnanes / Q000494:pharmacology; D011869:Radioligand Assay; D011955:Receptors, Drug / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase; D013329:Structure-Activity Relationship
D002316:Cardiotonic Agents; D005960:Glucosides; D008362:Mannosides; D011278:Pregnanes; D011955:Receptors, Drug; C027082:digitalis receptor; C078279:17-acetoxy-3-(glucopyransosyl)oxy-6-methylpregn-4-en-20-one; D010042:Ouabain; C045251:LND 623; D017258:Medroxyprogesterone Acetate; D000254:Sodium-Potassium-Exchanging ATPase; D008525:Medroxyprogesterone; D011188:Potassium