Steroids, intracellular sodium levels, and Na+/K+-ATPase regulation.
In outer medullary kidney tubules, both specific mineralocorticoid, and specific glucocorticoid Na+/K+-ATPase activation in vitro were inhibitable by amiloride, an inhibitor of a number of Na+-transporting mechanisms (Bentley, P.J. (1968) J. Physiol. (Lond.) 195, 317-330; Kinsella, J. L., and Aronson, P. S. (1980) Am. J. Physiol. 238, F461-F469). In addition, dexamethasone raised, whereas amiloride reduced, intracellular Na+ levels. These observations are consistent with the possibility that the steroidal responses are mediated by changes in intracellular Na+ ion activity. However, when intracellular Na+ levels were increased by the incubation of tubule segments in medium containing ouabain (10(-4) M), no Na+/K+-ATPase activation was observed, over incubation periods of up to 6 h. As mineralocorticoid and glucocorticoid effects are maximal within 2 h (Rayson, B.M., and Lowther, S.O. (1984) Am. J. Physiol. 246, F656-F662), these results suggest that the Na+ ion per se does not mediate the steroidal effects observed, directly. Incubation of tubule segments in medium containing 10(-4) M ouabain, at 37 degrees C, for longer periods (18 h), however, did indeed increase Na+/K+-ATPase activity, markedly. Thus, a potential homeostatic mechanism was demonstrable, where a chronic increase in intracellular Na+ level, measured after 2-4 h of treatment, resulted in an increase in Na+/K+-ATPase activity, such that the intracellular Na+ level was restored after 18-20 h of incubation to one not significantly different from the control value. This mechanism, however, appears to be clearly distinguishable from that which mediates steroidal Na+/K+-ATPase activation.
D000450:Aldosterone / Q000494:pharmacology; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D007679:Kidney Medulla / Q000378:metabolism*; D007684:Kidney Tubules / Q000378:metabolism*; D007685:Kidney Tubules, Collecting / Q000378:metabolism; D007686:Kidney Tubules, Distal / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008901:Mineralocorticoids / Q000494:pharmacology*; D010042:Ouabain / Q000494:pharmacology; D051381:Rats; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism*
D005938:Glucocorticoids; D008901:Mineralocorticoids; D000450:Aldosterone; D010042:Ouabain; D000584:Amiloride; D003907:Dexamethasone; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase