Mechanisms of AT1a receptor-mediated uptake of angiotensin II by proximal tubule cells: a novel role of the multi-ligand endocytic receptor megalin.

Mechanisms of AT1a receptor-mediated uptake of angiotensin II by proximal tubule cells: a novel role of the multi-ligand endocytic receptor megalin. Am J Physiol Renal Physiol. 2014 Apr 16; Authors: Li XC, Zhuo JL Abstract The present study tested the hypothesis that the multi-ligand endocytic receptor megalin is partially involved in the uptake of angiotensin II (ANG II) and downstream signaling responses in mouse proximal tubule cells (mPCT) by interacting with AT1a receptors. mPCT cells of wild-type (WT) and AT1a receptor-deficient (AT1a-KO) mice were treated with vehicle, the AT1 receptor blocker losartan (10 µM), or a selective megalin siRNA for 48 h. The uptake of fluorescein (FITC)-labeled ANG II (10 nM, 37(o)C) and downstream signaling responses were analyzed by fluorescence imaging and western blot. AT1a receptors and megalin were abundantly expressed in mPCT cells, whereas AT1a receptors were absent in AT1a-KO mPCT cells (P<0.01). In WT mPCT cells, the FITC-ANG II uptake was visualized at 30 min in the cytoplasm and in the nuclei 1 h after exposure. Losartan alone completely blocked the uptake of FITC-ANG II, whereas megalin siRNA inhibited only 30% of the response (P<0.01). The remaining FITC-ANG II uptake in the presence of megalin siRNA was completely abolished by losartan. ANG II induced 3-fold increases in phosphorylated MAP kinases ERK1/2 and one-fold increase in phosphorylated NHE3 proteins, which were also bl...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research