Terris J, Ecelbarger C A, Nielsen S, Knepper M A
Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung, and Blood Institute, Bethesda, Maryland 20892, USA.
Am J Physiol. 1996 Aug;271(2 Pt 2):F414-22. doi: 10.1152/ajprenal.1996.271.2.F414.
The aquaporins are molecular water channels expressed in the kidney and other organs. To investigate long-term regulation of renal expression of these water channels, we carried out immunoblotting studies using membrane fractions from rat renal cortex and medulla. Both 48-h water restriction in Sprague-Dawley rats and 5-day arginine vasopressin (AVP) infusion in Brattleboro rats caused significant increases in the expression levels of two aquaporins, aquaporin-2 and aquaporin-3, while the levels of aquaporin-1 and aquaporin-4 were unchanged. The increases in aquaporin-2 and aquaporin-3 expression were seen in inner and outer medulla as well as cortex. Ablation of the corticomedullary interstitial osmotic gradient with an infusion of furosemide did not eliminate the upregulatory response to AVP infusion in Brattleboro rats. Furthermore, 5-day furosemide infusion to Sprague-Dawley rats did not decrease expression levels of the collecting duct aquaporins, but rather increased them. We conclude that the expression of aquaporin-2 and aquaporin-3, but not aquaporin-1 or aquaporin-4, is increased in response to elevated circulating AVP. Because regulation of aquaporin-2 and aquaporin-3 levels was observed in the cortex and because osmotic gradient ablation did not abrogate the increase, we conclude that changes in interstitial osmolality are not necessary for the AVP-induced upregulation of aquaporin-2 and aquaporin-3 expression.
水通道蛋白是在肾脏和其他器官中表达的分子水通道。为了研究这些水通道蛋白在肾脏中的长期表达调控，我们使用大鼠肾皮质和髓质的膜组分进行了免疫印迹研究。在斯普拉格-道利大鼠中进行48小时的限水以及在布拉特洛维大鼠中输注5天的精氨酸加压素（AVP），均导致两种水通道蛋白——水通道蛋白-2和水通道蛋白-3的表达水平显著升高，而水通道蛋白-1和水通道蛋白-4的水平未发生变化。水通道蛋白-2和水通道蛋白-3表达的增加在内髓质、外髓质以及皮质中均可见。通过输注呋塞米消除皮质髓质间质渗透梯度，并未消除布拉特洛维大鼠对AVP输注的上调反应。此外，对斯普拉格-道利大鼠输注5天的呋塞米并未降低集合管水通道蛋白的表达水平，反而使其升高。我们得出结论，循环中AVP升高会导致水通道蛋白-2和水通道蛋白-3的表达增加，而水通道蛋白-1或水通道蛋白-4则不会。由于在皮质中观察到了水通道蛋白-2和水通道蛋白-3水平的调控，并且渗透梯度消除并未消除这种增加，我们得出结论，间质渗透压的变化对于AVP诱导的水通道蛋白-2和水通道蛋白-3表达上调并非必要条件。
