The renal subcellular distribution of various subcutaneous doses (10-10-10-8 mol) of [3H]aldosterone has been investigated in adrenalectomized rats pretreated with carbenoxolone. Carbenoxolone increased the concentration of plasma [3H]aldosterone, but the uptake of [3H]aldosterone into the kidney nuclear and cytosol fractions was decreased. Pretreatment of rats with carbenoxolone at low doses of aldosterone (0.4x10-10 and 1.5x10-10 mol) decreased both the amount of [3H]aldosterone bound to the 50% (NH4)2SO4 precipitate, and that present in the supernatant fraction, of a Tris-CaCl2 extract of the kidney nuclear fraction. Carbenoxolone also decreased the rate of biliary excretion of metabolites of aldosterone. When [3H]aldosterone and carbenoxolone were incubated with Tris-CaCl2 extracts of a kidney nuclear fraction in vitro, the carbenoxolone did not decrease the [3]aldosterone bound to the 50% (NH4)2SO4 precipitate, although the [3H]aldosterone bound to the 50% (NH4)2SO4 supernatant was significantly decreased by carbenoxolone at concentrations known to occur in the kidney in vivo. these results indicate that displacement of aldosterone from binding sites, with a concomitant potential increase in the amount of hormone available to specific receptors may be part of the machanism by which carbenoxolone potentiates aldosterone action in toad skin in vitro. However, in rat kidney, such a mechanism is unlikely to play a significant role in the manifestation by carbenoxolone of aldosterone-like effects. Data are presented to indicate that carbenoxolone may affect the normal distribution amd metabolism of aldosterone, and it is possible that potentiation of aldosterone action may involve receptors in other tissues, such as the gastrointestinal tract which is the major site of action of carbenoxolone.
