Chronic Regulation of the Renal Na+/H+ Exchanger NHE3 by Dopamine: Translational and Post-Translational Mechanisms.

Chronic Regulation of the Renal Na+/H+ Exchanger NHE3 by Dopamine: Translational and Post-Translational Mechanisms. Am J Physiol Renal Physiol. 2013 Feb 20; Authors: Hu MC, Di Sole F, Zhang J, McLeroy P, Moe OW Abstract The intrarenal autocrine/paracrine dopamine (DA) system contributes to natriuresis in response to both acute and chronic Na(+) loads. While the acute DA effect is well described, how DA induces natriuresis chronically is not known. We used an animal and a cell culture model to study the chronic effect of DA on a principal renal Na(+) transporter, Na(+)/H(+) exchanger-3 (NHE3). Intraperitoneal injection of gludopa in rats for 2 days elevated DA excretion and decreased total renal cortical and apical brush border NHE3 antigen. Chronic treatment of an opossum renal proximal cell line with DA decreased NHE3 activity, cell surface and total cellular NHE3 antigen, but not NHE3 transcript. The decrease in NHE3 antigen was dose- and time-dependent with maximal inhibition 16-24 hrs and half maximal effect at 3 x 10(-7) M. This is in contradistinction to the acute effect of DA on NHE3 (half maximal at 2 x 10(-6) M) which was not associated with changes in total cellular NHE3 protein. The DA-induced decrease in total NHE3 protein was associated with decrease in NHE3 translation and mediated by cis-sequences in the NHE3 5'-untranslated region. DA also decreased cell surface and total cellular NHE3 protein half-life. The DA-induced decrease...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research