Effects of 3'deoxyadenosine and actinomycin D on RNA synthesis in toad bladder: analysis of response to aldosterone.
Previous studies have shown that aldosterone increases transepithelial active Na+ transport after a latent period of about 60 min and incorporation of 3H-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 toad Bufo marinus. 3'deoxyadenosine (30 microgram/ml) only partially, though significantly, inhibited the aldosterone-dependent increase in Na+ transport measured as short-circuit current (scc). The incorporation of 3H-uridine into poly(A) (+)RNA was inhibited by 70 to 80%. In contrast, Actinomycin D (2 microgram/ml) totally inhibited the aldosterone-dependent increase in scc, and the incorporation of 3H-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-dpendent 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.
D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002024:Bufo marinus; D003609:Dactinomycin / Q000494:pharmacology*; D003839:Deoxyadenosines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis*; D012964:Sodium / Q000378:metabolism*; D013997:Time Factors; D001743:Urinary Bladder / Q000378:metabolism
D003839:Deoxyadenosines; D012333:RNA, Messenger; D003609:Dactinomycin; D000450:Aldosterone; D012964:Sodium