Sands Jeff M, Blount Mitsi A, Klein Janet D
Emory University School of Medicine, Renal Division, 1639 Pierce Drive, NE, WMB Room 338, Atlanta, GA 30322, USA.
Trans Am Clin Climatol Assoc. 2011;122:82-92.
Terrestrial life would be miserable without the ability to concentrate urine. Production of concentrated urine requires complex interactions among the nephron segments and vasculature in the kidney medulla. In addition to water channels (aquaporins) and sodium transporters, urea transporters are critically important to the theories proposed to explain the physiologic processes occurring when urine is concentrated. Vasopressin (anti-diuretic hormone) is the key hormone regulating the production of concentrated urine. Vasopressin rapidly increases water and urea transport in the terminal inner medullary collecting duct (IMCD). Vasopressin rapidly increases urea permeability in the IMCD through increases in phosphorylation and apical plasma-membrane accumulation of the urea transporter A1 (UT-A1). Vasopressin acts through two cAMP-dependent signaling pathways in the IMCD: protein kinase A and exchange protein activated by cAMP Epac. Protein kinase A phosphorylates UT-A1 at serines 486 and 499. In summary, vasopressin regulates urea transport acutely by increasing UT-A1 phosphorylation and the apical plasma-membrane accumulation of UT-A1 through two cAMP-dependent pathways.
如果没有浓缩尿液的能力，陆生生物的生活会很悲惨。产生浓缩尿液需要肾单位各节段与肾髓质血管系统之间进行复杂的相互作用。除了水通道（水孔蛋白）和钠转运蛋白外，尿素转运蛋白对于解释尿液浓缩时发生的生理过程所提出的理论至关重要。血管加压素（抗利尿激素）是调节浓缩尿液生成的关键激素。血管加压素可迅速增加终末内髓集合管（IMCD）中的水和尿素转运。血管加压素通过增加尿素转运蛋白A1（UT-A1）的磷酸化和顶端质膜积累，迅速增加IMCD中的尿素通透性。血管加压素通过IMCD中的两条cAMP依赖性信号通路发挥作用：蛋白激酶A和由cAMP激活的交换蛋白Epac。蛋白激酶A使UT-A1的丝氨酸486和499磷酸化。总之，血管加压素通过两条cAMP依赖性途径增加UT-A1磷酸化和UT-A1顶端质膜积累，从而急性调节尿素转运。
