Asher C, Wald H, Rossier B C, Garty H
Department of Membrane Research and Biophysics, Weizmann Institute of Science, Rehovot, Israel.
Am J Physiol. 1996 Aug;271(2 Pt 1):C605-11. doi: 10.1152/ajpcell.1996.271.2.C605.
The highly selective, amilorideblockable Na+ channel is a major target to the natriferic action of the mineralocorticoid aldosterone. This rat epithelial Na+ channel (rENaC) has been recently cloned from colon and is composed of three homologous subunits denoted alpha-, beta-, and gamma-rENaC (C. M. Canessa, L. Schild, G. Buell, B. Thorens, L. Gautschi, J.-D. Horisberger, and B. C. Rossier. Nature Lond. 367: 463-467, 1994). We have tested the effects of corticosteroids on the abundance of mRNA coding for each subunit in kidney cortex and distal colon. Chronic treatment of rats with aldosterone or dexamethasone evoked in kidney cortex a small induction of alpha-rENaC and no change in beta- and gamma-rENaC. In distal colon, however, beta- and gamma-rENaC were strongly induced by either aldosterone or dexamethasone, whereas alpha-rENaC was constitutively expressed. Most of the aldosterone-induced increase in beta- and gamma-rENaC mRNA took place during 3-24 h after plasma aldosterone was elevated. A similar differential induction of rENaC subunits in kidney and colon was also evoked by a Na(+)-free diet. The effects of salt deprivation were reversed by resalinating rats with a half time of < 2 h, suggesting a high turnover rate of at least beta- and gamma-rENaC. The data are consistent with the possibility that induction of channel subunits contributes to the chronic but not the acute response to aldosterone in the colon. Such a mechanism is not likely to play a major role in cortical collecting ducts.
高选择性、可被氨氯吡咪阻断的钠离子通道是盐皮质激素醛固酮促钠作用的主要靶点。这种大鼠上皮钠离子通道（rENaC）最近已从结肠中克隆出来，由三个同源亚基组成，分别称为α-rENaC、β-rENaC和γ-rENaC（C.M.卡内萨、L.希尔德、G.比尔、B.托伦斯、L.高茨基、J.-D.霍里斯贝格尔和B.C.罗西耶。《自然》伦敦版367:463 - 467，1994）。我们测试了皮质类固醇对肾皮质和远端结肠中编码各亚基的mRNA丰度的影响。用醛固酮或地塞米松对大鼠进行慢性处理，在肾皮质中引起α-rENaC少量诱导，而β-rENaC和γ-rENaC无变化。然而，在远端结肠中，醛固酮或地塞米松均可强烈诱导β-rENaC和γ-rENaC，而α-rENaC则持续表达。醛固酮诱导的β-rENaC和γ-rENaC mRNA增加大多发生在血浆醛固酮升高后的3 - 24小时内。无钠饮食也能在肾和结肠中引起rENaC亚基类似的差异诱导。通过给大鼠重新补充盐分，<2小时的半衰期可逆转盐缺乏的影响，这表明至少β-rENaC和γ-rENaC有很高的更新率。这些数据与通道亚基的诱导有助于结肠对醛固酮的慢性而非急性反应这一可能性一致。这种机制在皮质集合管中不太可能起主要作用。
