Aldosterone increases the apical Na+ permeability of toad bladder by two different mechanisms.
The aldosterone-induced augmentation of Na+ transport in toad bladder was analyzed by comparing the hormonal actions on the transepithelial short-circuit current and on the amiloride-sensitive 22Na+ uptake in isolated membrane vesicles. Incubating bladders with 0.5 microM aldosterone for 3 hr evoked more than a 2-fold increase of the short-circuit current (because of the activation or insertion of apical amiloride-blockable channels) but had no effect on the amiloride-sensitive Na+ transport in apical vesicles derived from the treated tissue. A longer incubation (e.g., 6 hr) produced an additional augmentation of the short-circuit current, which was accompanied by about a 3-fold increase of the channel activity in isolated membranes. The stimulatory effect of aldosterone sustained in vesicles was inhibited by the antagonist spironolactone (present at 1000-fold excess) and the protein synthesis inhibitor cycloheximide (1 microM). In addition, triiodothyronine and butyrate, previously reported to partly inhibit the aldosterone-induced increase in short-circuit current, blocked the hormonal effect in vesicles. It is suggested that aldosterone elevates the apical Na+ permeability of target epithelia by two different mechanisms: a relatively fast effect (less than or equal to 3 hr), which is insensitive to triiodothyronine or butyrate and is not sustained by the isolated membrane, and a slower or later (greater than 3 hr) response blocked by these reagents, which is preserved by the isolated membrane. The data also indicate that these processes are mediated by different nuclear receptors.
D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D002024:Bufo marinus; D002087:Butyrates / Q000494:pharmacology; D020148:Butyric Acid; D002463:Cell Membrane Permeability / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D008297:Male; D012413:Rubidium / Q000493:pharmacokinetics; D012964:Sodium / Q000493:pharmacokinetics*; D014284:Triiodothyronine / Q000494:pharmacology; D001743:Urinary Bladder / Q000187:drug effects* / Q000378:metabolism
D002087:Butyrates; D014284:Triiodothyronine; D020148:Butyric Acid; D000450:Aldosterone; D003907:Dexamethasone; D012964:Sodium; D012413:Rubidium