Steroid regulation of Na+-K+-ATPase: differential sensitivities along the nephron.

Steroid hormonal activation of the Na+-K+-ATPase enzyme was examined in enriched preparations of outer medullary collecting tubules (MCT) and outer medullary thick ascending limbs of the loop of Henle (MAL), prepared by sedimentation through a discontinuous Ficoll gradient. Using morphological criteria, there was a 2.9-fold enrichment of MCT in fraction 1 when compared with fraction 2 and a 2.2-fold enrichment of MAL in fraction 2 when compared with fraction 1. This separation was further defined using biochemical markers. Na+-K+-ATPase activity, Mg2+-ATPase activity, and the adenylate cyclase response to a number of hormones each supported the morphologic definition of separation. The two preparations were challenged in vitro with both aldosterone and dexamethasone. In fraction 1, the fraction enriched in the MCT, 10(-8) M aldosterone stimulated Na+-K+-ATPase activity by 37%. The same concentration of dexamethasone was without effect. In contrast, 10(-8) M dexamethasone stimulated Na+-K+-ATPase activity by 27% in fraction 2, the fraction enriched in the MAL. In this fraction an equimolar concentration of aldosterone was without effect. Thus, the regulation of Na+-K+-ATPase activity by mineralocorticoids on the one hand and by glucocorticoids on the other would appear to be discontinuously localized along the length of the outer medullary distal nephron.