Metabolism
Renal Proteinase-activated Receptor 2, a New Actor in the Control of Blood Pressure and Plasma Potassium Level*

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Proteinase-activated receptor 2 (PAR2) is a G protein-coupled membrane receptor that is activated upon cleavage of its extracellular N-terminal domain by trypsin and related proteases. PAR2 is expressed in kidney collecting ducts, a main site of control of Na+ and K+ homeostasis, but its function remains unknown. We evaluated whether and how PAR2 might control electrolyte transport in collecting ducts, and thereby participate in the regulation of blood pressure and plasma K+ concentration. PAR2 is expressed at the basolateral border of principal and intercalated cells of the collecting duct where it inhibits K+ secretion and stimulates Na+ reabsorption, respectively. Invalidation of PAR2 gene impairs the ability of the kidney to control Na+ and K+ balance and promotes hypotension and hypokalemia in response to Na+ and K+ depletion, respectively. This study not only reveals a new role of proteases in the control of blood pressure and plasma potassium level, but it also identifies a second membrane receptor, after angiotensin 2 receptor, that differentially controls sodium reabsorption and potassium secretion in the late distal tubule. Conversely to angiotensin 2 receptor, PAR2 is involved in the regulation of sodium and potassium balance in the context of either stimulation or nonstimulation of the renin/angiotensin/aldosterone system. Therefore PAR2 appears not only as a new actor of the aldosterone paradox, but also as an aldosterone-independent modulator of blood pressure and plasma potassium.

Aldosterone
Kidney
Potassium Transport
Protease
Sodium Transport
Blood Pressure
Plasma Potassium Concentration
Proteinase-activated Receptor

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*

This work was supported in part by grants from Amgen (2005/29-N), the Société de Néphrologie, the Agence Nationale de la Recherche (ANR-06-PHYSIO-035-01), and the Fondation Leducq.