Rayson B M, Gupta R K
J Biol Chem. 1985 Oct 15;260(23):12740-3.
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.
在肾外髓质肾小管中，特异性盐皮质激素和特异性糖皮质激素在体外对Na+/K+-ATP酶的激活作用均可被氨氯吡脒抑制，氨氯吡脒是多种Na+转运机制的抑制剂（本特利，P.J.（1968年）《生理学杂志》（伦敦）195卷，317 - 330页；金塞拉，J.L.，和阿隆森，P.S.（1980年）《美国生理学杂志》238卷，F461 - F469页）。此外，地塞米松可提高细胞内Na+水平，而氨氯吡脒则降低细胞内Na+水平。这些观察结果与甾体反应可能由细胞内Na+离子活性变化介导的可能性一致。然而，当通过在含有哇巴因（10(-4)M）的培养基中孵育肾小管节段来提高细胞内Na+水平时，在长达6小时的孵育期内未观察到Na+/K+-ATP酶激活。由于盐皮质激素和糖皮质激素的作用在2小时内达到最大值（雷森，B.M.，和洛瑟，S.O.（1984年）《美国生理学杂志》246卷，F656 - F662页），这些结果表明，Na+离子本身并不直接介导所观察到的甾体效应。然而，在37℃下，将肾小管节段在含有10(-4)M哇巴因的培养基中孵育更长时间（18小时），确实显著增加了Na+/K+-ATP酶活性。因此，一种潜在的稳态机制是可证明的，即在处理2 - 4小时后测量的细胞内Na+水平的慢性升高导致Na+/K+-ATP酶活性增加，使得在孵育18 - 20小时后细胞内Na+水平恢复到与对照值无显著差异的水平。然而，这种机制似乎与介导甾体Na+/K+-ATP酶激活的机制明显不同。
