| Entry |
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| Name |
Aldosterone-regulated sodium reabsorption - Ornithorhynchus anatinus (platypus)
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| 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.
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| Class |
Organismal Systems; Excretory system
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| Pathway map |
| Aldosterone-regulated sodium reabsorption |

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| Organism |
Ornithorhynchus anatinus (platypus) [GN: oaa]
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| Gene |
| corticosteroid 11-beta-dehydrogenase isozyme 2-like; K00071 corticosteroid 11-beta-dehydrogenase isozyme 2 [EC:1.1.1.-] [KO: K00071] [EC:1.1.1.-] | | mineralocorticoid receptor-like; K08555 mineralocorticoid receptor [KO: K08555] | | SCNN1A; sodium channel, non-voltage-gated 1 alpha subunit [KO: K04824] | | SCNN1B; sodium channel, non-voltage-gated 1, beta subunit [KO: K04825] | | amiloride-sensitive sodium channel subunit gamma-like; K04827 amiloride-sensitive sodium channel subunit gamma [KO: K04827] | | SGK1; serum/glucocorticoid regulated kinase 1 [KO: K13302] [EC: 2.7.11.1] | | ATP-sensitive inward rectifier potassium channel 1-like; K04995 potassium inwardly-rectifying channel subfamily J member 1 [KO: K04995] | | 14-3-3 protein sigma-like; K06644 stratifin [KO: K06644] | | GTPase KRas-like; K07827 GTPase KRas [KO: K07827] | | sodium/potassium-transporting ATPase subunit beta-1-like; K01540 sodium/potassium-transporting ATPase subunit beta [KO: K01540] | | sodium/potassium-transporting ATPase subunit beta-3-like; K01540 sodium/potassium-transporting ATPase subunit beta [KO: K01540] | | protein ATP1B4-like; K01540 sodium/potassium-transporting ATPase subunit beta [KO: K01540] | | insulin-like growth factor I-like; K05459 insulin-like growth factor 1 [KO: K05459] | | | | insulin receptor substrate 1-like; K16172 insulin receptor substrate 1 [KO: K16172] | | phosphoinositide 3-kinase regulatory subunit 5-like; K02649 phosphoinositide-3-kinase, regulatory subunit [KO: K02649] | | PIK3R2; phosphoinositide-3-kinase, regulatory subunit 2 (beta) [KO: K02649] | | phosphatidylinositol 3-kinase regulatory subunit alpha-like; K02649 phosphoinositide-3-kinase, regulatory subunit [KO: K02649] | | phosphatidylinositol 3-kinase regulatory subunit gamma-like; K02649 phosphoinositide-3-kinase, regulatory subunit [KO: K02649] | | PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit beta [KO: K00922] [EC: 2.7.1.153] | | | | | | 3-phosphoinositide-dependent protein kinase 1-like; K06276 3-phosphoinositide dependent protein kinase-1 [EC: 2.7.11.1] [KO: K06276] [EC: 2.7.11.1] | | | | mitogen-activated protein kinase 1-like; K04371 extracellular signal-regulated kinase 1/2 [EC: 2.7.11.24] [KO: K04371] [EC: 2.7.11.24] |
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| Compound |
| Potassium cation | | 3',5'-Cyclic AMP | | Cl- | | Cortisol | | Cortisone | | Sodium cation | | Aldosterone | | Phosphatidylinositol-3,4,5-trisphosphate |
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| Reference |
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| Authors |
Connell JM, Davies E |
| Title |
The new biology of aldosterone. |
| Journal |
J Endocrinol 186:1-20 (2005) |
| Reference |
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| Authors |
Booth RE, Johnson JP, Stockand JD |
| Title |
Aldosterone. |
| Journal |
Adv Physiol Educ 26:8-20 (2002) |
| Reference |
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| Authors |
Lee IH, Campbell CR, Cook DI, Dinudom A |
| Title |
Regulation of epithelial Na+ channels by aldosterone: role of Sgk1. |
| Journal |
Clin Exp Pharmacol Physiol 35:235-41 (2008) |
| Reference |
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| 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 |
Nucl Recept Signal 5:e012 (2007) |
| Reference |
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| Authors |
Fuller PJ, Young MJ |
| Title |
Mechanisms of mineralocorticoid action. |
| Journal |
Hypertension 46:1227-35 (2005) |
| Reference |
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| 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 |
Cell Physiol Biochem 13:21-8 (2003) |
| Reference |
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| Authors |
Pearce D, Kleyman TR |
| Title |
Salt, sodium channels, and SGK1. |
| Journal |
J Clin Invest 117:592-5 (2007) |
| Reference |
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| Authors |
Grossmann C, Gekle M |
| Title |
New aspects of rapid aldosterone signaling. |
| Journal |
Mol Cell Endocrinol 308:53-62 (2009) |
| Reference |
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| 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 |
Am J Physiol Regul Integr Comp Physiol 288:R4-10 (2005) |
| Reference |
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| Authors |
Rogerson FM, Brennan FE, Fuller PJ |
| Title |
Dissecting mineralocorticoid receptor structure and function. |
| Journal |
J Steroid Biochem Mol Biol 85:389-96 (2003) |
| Reference |
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| 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 |
Am J Physiol Renal Physiol 280:F303-13 (2001) |
| Reference |
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| Authors |
Good DW |
| Title |
Nongenomic actions of aldosterone on the renal tubule. |
| Journal |
Hypertension 49:728-39 (2007) |
| KO pathway |
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