Cordycepin and alpha-amanitin: inhibitors of transcription as probes of aldosterone action.

Abstract

Evidence has been presented for the existence of distinct RNA polymerases (I and II) in the rat kidney similar to those described previously in rat liver and identified as nucleolar (I) and nucleoplasmic (II) in location. In adrenalectomized rats, administration of d-aldosterone (1 μg/100 g body wt) increased the ratio of polymerase I∶II activity as defined by sensitivity to α-amanitin. The time-course of this shift correlated with the previously reported changes in urinary Na and K concentrations, in that a significant change in the I∶II ratio was noted 1 to 2 hr before the usual peak change in urinary electrolyte concentrations. In the isolated urinary bladder of the toad, cordycepin inhibited incorporation of3H-uridine into epithelial RNA — with a half time of 4.3 min - and impaired the action of aldosterone on transepithelial Na transport. These findings as well as earlier studies in the literature imply that aldosterone augments ribosomal RNA synthesis, and that ribosomal or messenger RNA synthesis or both are required for the expression of mineralocorticoid activity.