Entry Name Aldosterone-regulated sodium reabsorption - Homo sapiens (human)
Description Sodium transport across the tight epithelia of Na+ reabsorbing tissues such as the distal part of the kidney nephron and colon is the major factor determining total-body Na+ levels, and thus, long-term blood pressure. Aldosterone plays a major role in sodium and potassium metabolism by binding to epithelial mineralocorticoid receptors (MR) in the renal collecting duct cells localized in the distal nephron, promoting sodium resorption and potassium excretion. Aldosterone enters a target cell and binds MR, which translocates into the nucleus and regulates gene transcription. Activation of MR leads to increased expression of Sgk-1, which phosphorylates Nedd4-2, an ubiquitin-ligase which targets ENAC to proteosomal degradation. Phosphorylated Nedd4-2 dissociates from ENAC, increasing its apical membrane abundance. Activation of MR also leads to increased expression of Na+/K+-ATPase, thus causing a net increase in sodium uptake from the renal filtrate. The specificity of MR for aldosterone is provided by 11beta-HSD2 by the rapid conversion of cortisol to cortisone in renal cortical collecting duct cells. Recently, besides genomic effects mediated by activated MR, rapid aldosterone actions that are independent of translation and transcription have been documented.
Class Organismal Systems; Excretory systemBRITE hierarchy
Pathway map hsa04960 Aldosterone-regulated sodium reabsorption
Drug D00386 Triamterene (JP19/USP/INN)
D00443 Spironolactone (JP19/USP/INN)
D00649 Amiloride hydrochloride (USP)
D00986 Fludrocortisone acetate (JP19/USP)
D01115 Eplerenone (JP19/USAN/INN)
D01943 Canrenoate potassium (USAN)
D03698 Desoxycorticosterone acetate (USP)
D03699 Desoxycorticosterone pivalate (USP)
D05020 Mexrenoate potassium (USAN)
D05640 Prorenoate potassium (USAN/INN)
D10633 Finerenone (JAN/USAN/INN)
D11667 Miricorilant (USAN/INN)
D13184 Balcinrenone (JAN/USAN/INN)
Organism Homo sapiens (human) [GN:
hsa ]
Gene 3291 HSD11B2; 11-beta-hydroxysteroid dehydrogenase type 2 [KO:K00071 ] [EC:1.1.1.-]
3479 IGF1; insulin-like growth factor 1 isoform 3 preproprotein [KO:K05459 ]
3667 IRS1; insulin receptor substrate 1 [KO:K16172 ]
3758 KCNJ1; ATP-sensitive inward rectifier potassium channel 1 isoform a [KO:K04995 ]
4306 NR3C2; mineralocorticoid receptor isoform 1 [KO:K08555 ]
476 ATP1A1; sodium/potassium-transporting ATPase subunit alpha-1 isoform a [KO:K01539 ] [EC:7.2.2.13 ]
477 ATP1A2; sodium/potassium-transporting ATPase subunit alpha-2 precursor [KO:K01539 ] [EC:7.2.2.13 ]
478 ATP1A3; sodium/potassium-transporting ATPase subunit alpha-3 isoform 1 [KO:K01539 ] [EC:7.2.2.13 ]
480 ATP1A4; sodium/potassium-transporting ATPase subunit alpha-4 isoform 1 [KO:K01539 ] [EC:7.2.2.13 ]
481 ATP1B1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540 ]
482 ATP1B2; sodium/potassium-transporting ATPase subunit beta-2 isoform 1 [KO:K01540 ]
483 ATP1B3; sodium/potassium-transporting ATPase subunit beta-3 [KO:K01540 ]
486 FXYD2; sodium/potassium-transporting ATPase subunit gamma isoform 1 [KO:K01538 ]
5170 PDPK1; 3-phosphoinositide-dependent protein kinase 1 isoform 1 [KO:K06276 ] [EC:2.7.11.1 ]
5290 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
5291 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform 1 [KO:K00922 ] [EC:2.7.1.153 ]
5293 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform 1 [KO:K00922 ] [EC:2.7.1.153 ]
5295 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform 1 [KO:K02649 ]
5296 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
53828 FXYD4; FXYD domain-containing ion transport regulator 4 precursor [KO:K13359 ]
6337 SCNN1A; epithelial sodium channel subunit alpha isoform 1 [KO:K04824 ]
6338 SCNN1B; epithelial sodium channel subunit beta isoform 1 [KO:K04825 ]
6340 SCNN1G; epithelial sodium channel subunit gamma [KO:K04827 ]
8503 PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform 1 [KO:K02649 ]
9351 NHERF2; Na(+)/H(+) exchange regulatory cofactor NHE-RF2 isoform a [KO:K13358 ]
Compound C05981 Phosphatidylinositol-3,4,5-trisphosphate
Reference Authors Connell JM, Davies E
Title The new biology of aldosterone.
Journal Reference Authors Booth RE, Johnson JP, Stockand JD
Title Aldosterone.
Journal Reference Authors Lee IH, Campbell CR, Cook DI, Dinudom A
Title Regulation of epithelial Na+ channels by aldosterone: role of Sgk1.
Journal Reference Authors Viengchareun S, Le Menuet D, Martinerie L, Munier M, Pascual-Le Tallec L, Lombes M
Title The mineralocorticoid receptor: insights into its molecular and (patho)physiological biology.
Journal Reference Authors Fuller PJ, Young MJ
Title Mechanisms of mineralocorticoid action.
Journal Reference Authors Verrey F, Loffing J, Zecevic M, Heitzmann D, Staub O
Title SGK1: aldosterone-induced relay of Na+ transport regulation in distal kidney nephron cells.
Journal Reference Authors Pearce D, Kleyman TR
Title Salt, sodium channels, and SGK1.
Journal Reference Authors Grossmann C, Gekle M
Title New aspects of rapid aldosterone signaling.
Journal Reference Authors Vallon V, Wulff P, Huang DY, Loffing J, Volkl H, Kuhl D, Lang F
Title Role of Sgk1 in salt and potassium homeostasis.
Journal Reference Authors Rogerson FM, Brennan FE, Fuller PJ
Title Dissecting mineralocorticoid receptor structure and function.
Journal Reference Authors Wang J, Barbry P, Maiyar AC, Rozansky DJ, Bhargava A, Leong M, Firestone GL, Pearce D
Title SGK integrates insulin and mineralocorticoid regulation of epithelial sodium transport.
Journal Reference Authors Good DW
Title Nongenomic actions of aldosterone on the renal tubule.
Journal Related KO pathway
