title: Renal proteinase-activated receptor 2, a new actor in the control of blood pressure and plasma potassium level.
abstract: 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.
authors: Centre de Recherche des Cordeliers, Université Pierre et Marie Curie, Université Paris-Descartes, INSERM (UMRS872) and Centre National de la Recherche Scientifique (ERL7226), 75270 Paris cedex 06.
authors: Luciana
authors: L
authors: Morla
authors: Centre de Recherche des Cordeliers, Université Pierre et Marie Curie, Université Paris-Descartes, INSERM (UMRS872) and Centre National de la Recherche Scientifique (ERL7226), 75270 Paris cedex 06.
authors: Gaëlle
authors: G
authors: Brideau
authors: Centre de Recherche des Cordeliers, Université Pierre et Marie Curie, Université Paris-Descartes, INSERM (UMRS872) and Centre National de la Recherche Scientifique (ERL7226), 75270 Paris cedex 06.
authors: Marc
authors: M
authors: Fila
authors: Centre de Recherche des Cordeliers, Université Pierre et Marie Curie, Université Paris-Descartes, INSERM (UMRS872) and Centre National de la Recherche Scientifique (ERL7226), 75270 Paris cedex 06.
authors: Gilles
authors: G
authors: Crambert
authors: Centre de Recherche des Cordeliers, Université Pierre et Marie Curie, Université Paris-Descartes, INSERM (UMRS872) and Centre National de la Recherche Scientifique (ERL7226), 75270 Paris cedex 06.
authors: Lydie
authors: L
authors: Cheval
authors: Centre de Recherche des Cordeliers, Université Pierre et Marie Curie, Université Paris-Descartes, INSERM (UMRS872) and Centre National de la Recherche Scientifique (ERL7226), 75270 Paris cedex 06; Faculté de Médecine, Université Paris-Descartes, 75006 Paris; Département de Physiologie, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, 75004 Paris, France.
authors: Pascal
authors: P
authors: Houillier
authors: Centre de Recherche des Cordeliers, Université Pierre et Marie Curie, Université Paris-Descartes, INSERM (UMRS872) and Centre National de la Recherche Scientifique (ERL7226), 75270 Paris cedex 06.
authors: Sureshkrishna
authors: S
authors: Ramakrishnan
authors: Centre de Recherche des Cordeliers, Université Pierre et Marie Curie, Université Paris-Descartes, INSERM (UMRS872) and Centre National de la Recherche Scientifique (ERL7226), 75270 Paris cedex 06.
authors: Martine
authors: M
authors: Imbert-Teboul
authors: Centre de Recherche des Cordeliers, Université Pierre et Marie Curie, Université Paris-Descartes, INSERM (UMRS872) and Centre National de la Recherche Scientifique (ERL7226), 75270 Paris cedex 06. Electronic address: alain.doucet@crc.jussieu.fr.
authors: Alain
authors: A
authors: Doucet
mesh_terms: D000450:Aldosterone / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure; D002118:Calcium / Q000378:metabolism; D004232:Diuretics / Q000494:pharmacology; D005786:Gene Expression Regulation; D006706:Homeostasis; D007668:Kidney / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010477:Perfusion; D011188:Potassium / Q000097:blood*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044464:Receptor, PAR-2 / Q000378:metabolism*; D012964:Sodium / Q000097:blood*
chemical_list: D004232:Diuretics; D044464:Receptor, PAR-2; D000450:Aldosterone; D012964:Sodium; D011188:Potassium; D002118:Calcium