Specific activity of Na−K-ATPase after adrenalectomy and hormone replacement along the rabbit nephron
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Both aldosterone and dexamethasone are known to stimulate renal Na−K-ATPase activity although their action is restricted to specific nephron segments: the collecting tubule, the target site for mineralocorticoids, and the thick ascending limb and distal convoluted tubule, the target sites for glucocorticoids. As this stimulation by corticosteroids is very fast, we attempted to establish whether it occurs through de novo synthesis of new Na−K-ATPase units or by increasing the specific activity of the Na−K-ATPase units already present.
For this purpose we studied the effects of aldosterone and dexamethasone on Na−K-ATPase specific activity in microdissected nephron segments from adrenalectomized rabbits. This specific activity was determined by the ratio of ATPase activity over the apparent number of catalytic units, as measured by specific3H ouabain binding. In the proximal tubule, neither adrenalectomy nor steroid replacement altered Na−K-ATPase activity or the apparent number of catalytic sites. In other nephron segments, adrenalectomy reduced Na−K-ATPase activity and specific3H ouabain binding concomitantly, and therefore left this enzyme's specific activity unaltered. In the cortical and outer medullary collecting tubules, 10 μg/kg aldosterone simultaneously restored both the activity and apparent number of catalytic units of Na−K-ATPase to their control levels, and therefore did not modify the specific activity of the pump. Conversely, 100 μg/kg dexamethasone increased Na−K-ATPase activity in the thick ascending limb and distal convoluted tubule without changing the apparent number of catalytic units. These results indicate that both mineraloand glucocorticoids control kidney Na−K-ATPase activity, but at different sites and by different mechanisms: Aldosterone induces appearance of new catalytic units in the collecting tubule, whereas dexamethasone increases the specific activity of pre-existing units in the thick ascending limb and distal convoluted tubule.
Key wordsAdrenalectomized rabbit Kidney microdissection Mineralocorticoid and glucocorticoid effects 3H ouabain binding
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