title: (Pro)Renin receptor regulates potassium homeostasis through a local mechanism.
abstract: (Pro)renin receptor (PRR) is highly expressed in the distal nephron, but it has an unclear functional implication. The present study was conducted to explore a potential role of renal PRR during high K+(HK) loading. In normal Sprague-Dawley rats, a 1-wk HK intake increased renal expression of full-length PRR and urinary excretion of soluble PRR (sPRR). Administration of PRO20, a decoy peptide antagonist of PRR, in K+-loaded animals elevated plasma K+level and decreased urinary K+excretion, accompanied with suppressed urinary aldosterone excretion and intrarenal aldosterone levels. HK downregulated Na+-Cl-cotransporter (NCC) expression but upregulated CYP11B2 (cytochromeP-450, family 11, subfamily B, polypeptide 2), renal outer medullary K+channel (ROMK), calcium-activated potassium channel subunit α1(α-BK), α-Na+-K+-ATPase (α-NKA), and epithelial Na+channel subunit β (β-ENaC), all of which were blunted by PRO20. After HK loading was completed, urinary, but not plasma renin, was upregulated, which was blunted by PRO20. The same experiments that were performed using adrenalectomized (ADX) rats yielded similar results. Interestingly, spironolactone treatment in HK-loaded ADX rats attenuated kaliuresis but promoted natriuresis, which was associated with the suppressed responses of β-ENaC, α-NKA, ROMK, and α-BK protein expression. Taken together, we discovered a novel role of renal PRR in regulation of K+homeostasis through a local mechanism involving intrarenal renin-angiotensin-aldosterone system and coordinated regulation of membrane Na+- and K+-transporting proteins.
authors.affiliation: Institute of Hypertension, Sun Yat-sen University School of Medicine, Guangzhou, China.
authors.forename: Chuanming
authors.initials: C
authors.lastname: Xu
authors.affiliation: Institute of Hypertension, Sun Yat-sen University School of Medicine, Guangzhou, China.
authors.forename: Aihua
authors.initials: A
authors.lastname: Lu
authors.affiliation: Institute of Hypertension, Sun Yat-sen University School of Medicine, Guangzhou, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Institute of Hypertension, Sun Yat-sen University School of Medicine, Guangzhou, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Fang
authors.affiliation: Institute of Hypertension, Sun Yat-sen University School of Medicine, Guangzhou, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Anesthesiology, Sun Yat-sen University Cancer Center, Guangzhou, China; and.
authors.forename: Peng
authors.initials: P
authors.lastname: Sun
authors.affiliation: Institute of Hypertension, Sun Yat-sen University School of Medicine, Guangzhou, China; Tianxin.Yang@hsc.utah.edu.|Internal Medicine, University of Utah and Veterans Affairs Medical Center, Salt Lake City, Utah.
authors.forename: Tianxin
authors.initials: T
authors.lastname: Yang
mesh_terms: D000315:Adrenalectomy; D000450:Aldosterone / Q000378:metabolism; D000818:Animals; D019405:Cytochrome P-450 CYP11B2 / Q000378:metabolism; D004195:Disease Models, Animal; D053503:Epithelial Sodium Channels / Q000378:metabolism; D006706:Homeostasis; D006947:Hyperkalemia / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000652:urine; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000378:metabolism; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism; D017419:Potassium, Dietary; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012083:Renin / Q000494:pharmacology; D012084:Renin-Angiotensin System / Q000187:drug effects; D015398:Signal Transduction; D064486:Solute Carrier Family 12, Member 3 / Q000378:metabolism; D013148:Spironolactone / Q000494:pharmacology; D025262:Vacuolar Proton-Translocating ATPases; D000093342:Prorenin Receptor
chemical_list: D000450:Aldosterone; D019405:Cytochrome P-450 CYP11B2; D053503:Epithelial Sodium Channels; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D000451:Mineralocorticoid Receptor Antagonists; D010446:Peptide Fragments; D024661:Potassium Channels, Inwardly Rectifying; D017419:Potassium, Dietary; D006180:Proton-Translocating ATPases; D011956:Receptors, Cell Surface; D012083:Renin; D064486:Solute Carrier Family 12, Member 3; D013148:Spironolactone; D025262:Vacuolar Proton-Translocating ATPases; C510692:Kcnj1 protein, rat; C494842:Kcnma1 protein, rat; C000595796:PRO20 peptide; C507050:Scnn1b protein, rat; C578876:Slc12a3 protein, rat; C514240:ATP6AP2 protein, rat; D000093342:Prorenin Receptor
keywords: (Pro)renin receptor; CYP11B2; Na+-Cl− cotransporter; aldosterone; kidney; potassium