Effects of 3′deoxyadenosine and actinomycin D on RNA synthesis in toad bladder: Analysis of response to aldosterone

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Abstract
Previous studies have shown that aldosterone increases transepithelial active Na+ transport after a latent period of about 60 min and incorporation of3H-uridine into polyadenylated RNA (poly(A)(+)RNA) (putatively poly(A)(+)mRNA) as early as 30 min after aldosterone addition. To assess the physiological importance of this pathway, the effects of 3′deoxyadenosine and actinomycin D were compared in studies on the urinary bladder of the toadBufo marinus. 3′deoxyadenosine (30 μg/ml) only partially, though significantly, inhibited the aldosterone-dependent increase in Na+ transport measured as short-circuit current (scc). The incorporation of3H-uridine into poly(A) (+)RNA was inhibited by 70 to 80%. In contrast, Actinomycin D (2 μg/ml) totally inhibited the aldosterone-dependent increase in scc, and the incorporation of3H-uridine into poly(A)(+)RNA by 68 to 75%. 3′deoxyadenosine or actinomycin D alone had no significant effects on baseline scc, while inhibiting poly(A)(+)RNA to the same extent. The differential effects of deoxyadenosine and actinomycin on aldosterone-dependent Na+ transport may be related to their different sites of action on RNA synthesis: both drugs inhibited, to a similar extent, cytoplasmic poly(A)(+)mRNA; however, 3′deoxyadenosine, in contrast to Actinomycin D, failed to inhibit poly(A)(-)RNA, sedimenting between 4S and 18S (putatively poly(A)(-)mRNA). We conclude that the mineralocorticoid action of aldosterone during the first three hours depends on the synthesis of both poly(A)(+)mRNA and poly(A)(-)mRNA.