1577 ALDOSTERONE METABOLISM AND Na TRANSPORT

Abstract

Recent studies have demonstrated that aldosterone (aldo) is transformed into a number of metabolites by nuclei and plasma membranes of mammalian kidney cells (J. Steroid Biochem. 19:1205, 1983). In mammalian kidney, aldo not only promotes Na⁺ reabsorption but also secretion of K⁺ and H⁺. most probably reflecting functions of several cell types. In order to study the effects of transformation on Na⁺ transport alone, aldo metabolism was examined in a more elemental Na⁺ transporting aldo responsive epithelia, the toad urinary bladder (Bufo marinus). After depletion or endogenous aldo, bladders were incubated with ³H aldo for either 1 or 5 hrs. Tissues were analyzed for aldo metabolites using high resolution HPLC. In separate experiments, Na⁺ transport was assessed by the short circuit current (SSC) technique. After 1 hr of ³H aldo exposure (a latent period prior to an aldo induced rise in SCC) tissues transformed about 10% of the labelled hormone into a polar mono-sulfated aldo and a variety of 5-α reduced aldo products including 5α dihydroaldo (DHA); 3α,5α tetrahydroaldo (THA); and 3β, 5α THA. 5α DHA possess significant antinatriuretic activity in kidney and toad bladder. Following a 5 hr tissue incubation (a time of peak aldo rise in SCC). about 25% of the ³H aldo was converted into the same compounds as in the 1 hr study. The spironolactone, K-canrenoate (3.5 × 10⁻⁴M) inhibited aldo (10⁻⁷M) stimulated SCC by 56±6% (p<0.001; n=6) and eliminated ³H aldo metabolism at both 1 & 5 hrs. K-canrenoate had no effect on either basal or vasopressin stimulated rise in SCC. We conclude that aldo metabolic transformation begins prior to aldo induced increases in Na⁺ transport. Both the generation of aldo metabolites and the increase in Na⁺ transport can be selectively inhibited by K-canrenoate. We speculate that one or more of these aldo metabolites may mediate or regulate aldo action in this tissue.

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