Effect of various 6-dehydro-corticosteroids, 9, 11-dehydro-DOCA and 9 alpha-fluoro-DOCA on the fluxes of sodium and potassium.
The introduction of a double bond at carbons 6 and 7 (6-dehydro-derivatives) of deoxycorticosterone acetate (DOCA), cortisol-21-acetate, 9 alpha-fluorocortisol-21-acetate (9 alpha-F-C-ac) and aldosterone-21-acetate substantially reduces affinity for Type II receptors but not for Type I receptors. Such a modification changes the effect of these steroids on urinary excretion of Na+ and K+. 6-Dehydro-derivatives will thus bind preferentially to receptor Type I inducing the retention of sodium and compete with mineralocorticoids for such receptors. The increase in both natriuresis and kaliuresis when corticosteroids and their 6-dehydro-derivatives are administered together may be interpreted as evidence for a Type II receptor mediation of those ion fluxes. The ionic changes are not mediated by the (Na+ + K+)-ATPase system. The fluoration at 9 and the dehydrogenation at C9C11 of DOCA result in a strong increase of binding to Type I receptor and of sodium retention.
Genard
P
P
Institut de Chimie; CHU, Université de Liège.
Palem-Vliers
M
M
Christiaens
J M
JM
Krzesinski
J M
JM
Hacha
R
R
Lomba Pignon
M R
MR
D000315:Adrenalectomy; D000450:Aldosterone / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D003900:Desoxycorticosterone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000031:analogs & derivatives / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000201:enzymology; D008297:Male; D009318:Natriuresis / Q000187:drug effects*; D011188:Potassium / Q000652:urine*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D012414:Rubidium Radioisotopes / Q000097:blood; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D012414:Rubidium Radioisotopes; C060976:aldosterone-21-acetate; C044437:9-fluorodeoxycorticosterone; C021650:hydrocortisone acetate; D003900:Desoxycorticosterone; C060975:9,11-dehydrodeoxycorticosterone 21-acetate; D000450:Aldosterone; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium; D006854:Hydrocortisone