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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.
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| http://dx.doi.org/10.3109/13813458909104537 | DOI Listing |
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