Role of caveolin 1 in AT1a receptor-mediated uptake of angiotensin II in the proximal tubule of the kidney.

Role of caveolin 1 in AT1a receptor-mediated uptake of angiotensin II in the proximal tubule of the kidney. Am J Physiol Renal Physiol. 2014 Aug 27; Authors: Li XC, Gu V, Miguel-Qin E, Zhuo JL Abstract Caveolin 1 (CAV-1) functions not only as a constitutive scaffolding protein of caveolae but also as a vesicular transporter and signaling regulator. In the present study, we tested the hypothesis that CAV-1 knockout (CAV-1 KO) inhibits AT1 (AT1a) receptor-mediated uptake of angiotensin II (ANG II) in the proximal tubule and attenuates blood pressure responses in ANG II-induced hypertension. To determine the role of CAV-1 in mediating the uptake of fluorescein (FITC)-labeled ANG II, wild-type (WT) mouse PT cells (mPCT) were transfected with CAV-1 siRNA for 48 h before AT1a-mediated uptake of FITC-ANG II was studied. CAV-1 siRNA knocked down CAV-1 expression by >90% (P<0.01) and inhibited FITC-ANG II uptake by >50% (P<0.01). Moreover, CAV-1 siRNA attenuated ANG II-induced activation of MAP kinases ERK1/2 and the sodium and hydrogen exchanger 3, respectively (P<0.01). To determine whether CAV-1 regulates ANG II uptake in the proximal tubule, Alexa 488-labeled ANG II was infused into anesthetized WT and CAV-1 KO mice for 60 min (20 ng/min, i.v.). Imaging analysis revealed that Alexa 488-ANG II uptake was decreased by >50% in CAV-1 KO mice (P<0.01). Furthermore, Val5-ANG II was infused into WT and CAV-1 KO mice for 2 we...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research