The Activity Of NHE3 Regulated By Dopamine

Dopamine (dopamine, DA) plays a role in maintaining sodium and water homeostasis, it can regulate the glomerular filtration rate by controlling renal blood flow, it can also participate the control of reabsorption of water and salt in the proximal tubule. Dopamine may inhibit the activity of apical sodium hydrogen exchanger (NHE), chloride bicarbonate exchanger (CBE) and sodium phosphate cotransporter (NaPi-2) and the basolateral sodium-potassium ATPase (Na +- K+ -ATPase) and CBE, and leading to subsequent natriuresis and diuresis. Dopamine produced in the proximal tubule (PT) acts as an autocrine/paracrine natriuretic hormone that inhibits salt and fluid reabsorption in the PT, renal dopamine levels were significantly higher than that in circulating blood, suggests that renal dopamine is independent of the control of neuroendocrine, so it is presented that local dopamine hypothesis. The current study is an important contribution to the accumulating evidence that use of dopamine is not efficacious for renal protection.Luminal membrane Na+ / H+ exchange in the mammalian proximal tubule and thick ascending limb of loop mediates the isotonic reabsorption of approximately two thirds of the filtered NaCl and water, the reabsorption of bicarbonate, and the secretion of ammonium (NH4+ ) and contributes to the reabsorption of filtered citrate, amino acids, oligopeptides, and proteins. The expression and activity of renal NHE3 is regulated by many factors, such as acids, adenosine, angiotensin, aldosterone, etc. Now, the study of NHE3 activity regulated by dopamine focus on brain tissues and salivary glands, and more are from in vitro results, and less focuses on kidney and in vivo experiment, so the aim of this experiment mainly investigatest the role of renal dopamine on NHE3 trafficking.Objective:Because dopamine can be formed locally in proximal epithelial cells, and dopamine of renal origin exerts local natriuretic and diuretic effects. In this study, in order to studing the renal salt and water metabolism of local dopamine in physiological and pathological state, the regulation of local dopamine on NHE3 and sodium - potassium ATPase in the kidney. Methods:Wistar rats were divided into experimental group (dopa, n = 10) and control group (Control, n = 8), experimental rats was performed with intravenous infusion of low doses of levodopa (5μg / kg / min) 2 hours, The servo control system monitor the urine output and sodium in rats, and monitoring blood pressure, plasma osmolality and creatitine clearance rate were determined simultaneously, NHE3 and Na+ - K+ - ATPase expression was also detected RT-PCR and Western blotting. Results:With persistent intravenous infusion of low doses of levodopa, the blood pressure, plasma osmolality, and creatinine clearance rate has not changed in the dopa group the urine output significantly increased in experimental rats at 25 min after the administration, and the urinary sodium significantly increased at 30 min after administration. RT-PCR results showed that the level of NHE3 mRNA did not change with low doses of levodopa for two hours. But, western blotting result showed that membrane expression of NHE3 protein decreased, while cytoplasmic NHE3 increased slightly, the expression of sodium - potassium ATPase did not change in dopa group. Conclusion:Through persistent intravenous infusion of low doses of levodopa, locally formed dopamine in the kidney can play a diuretic and natriuretic effect. Local dopamine can induce the internalization of membrane NHE3 of renal proximal epithelial cell and promote the decreased absorption of sodium. Natriuresis of local dopamine induced was performed mainly through the regulation of transient trafficking of NHE3 and not by a long-term regulation. The rate-limiting reabsorption of sodium in proximal tubular cell was achieved by NHE3, and this action was supported by Na +- K+ - ATPase.