Bacic Desa, Kaissling Brigitte, McLeroy Paul, Zou Lixian, Baum Michel, Moe Orson W
Institute of Anatomy, University of Zürich, Zürich, Switzerland.
Kidney Int. 2003 Dec;64(6):2133-41. doi: 10.1046/j.1523-1755.2003.00308.x.
Dopamine is a principal natriuretic hormone in mammalian Na+ homeostasis. Dopamine acutely alters glomerular filtration rate (GFR) and decreases Na+ absorption in both the proximal and distal nephron. Proximal tubule natriuresis is effected through inhibition of the apical membrane Na/H exchanger NHE3.
We examined whether dopamine directly and acutely decreases apical membrane NHE3 protein using renal tissue in two in vitro systems: renal cortical slices and in vitro perfused single tubules. After incubation with dopamine, NHE3 activity was measured by 22Na flux and NHE3 antigen was measured by immunoblot in apical membrane and total cellular membranes.
Direct application of dopamine to either cortical slices or microperfused tubules acutely decreases NHE3 activity and antigen at the apical membrane of the proximal tubule. No change in total cellular NHE3 was detected.
One mechanism by which dopamine causes natriuresis is via direct and acute reduction of NHE3 protein at the apical membrane via changes in NHE3 protein trafficking.
多巴胺是哺乳动物钠稳态中的一种主要利钠激素。多巴胺可急性改变肾小球滤过率(GFR),并降低近端和远端肾单位的钠重吸收。近端小管利钠作用是通过抑制顶端膜钠/氢交换体NHE3来实现的。
我们在两种体外系统中使用肾组织,研究多巴胺是否直接且急性降低顶端膜NHE3蛋白:肾皮质切片和体外灌注的单肾小管。用多巴胺孵育后,通过22Na通量测量NHE3活性,通过免疫印迹法测量顶端膜和总细胞膜中的NHE3抗原。
将多巴胺直接应用于皮质切片或微灌注小管,可急性降低近端小管顶端膜的NHE3活性和抗原。未检测到总细胞NHE3有变化。
多巴胺引起利钠作用的一种机制是通过NHE3蛋白转运的变化,直接且急性地减少顶端膜的NHE3蛋白。