Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P41181 (collecting duct)
 5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aldosterone as a regulatory factor of extracellular volumes: mechanism of action. The key role assumed by aldosterone in the regulation of extracellular volumes, requires that chloride move along with sodium when active transport of the latter ion is stimulated. In the mammalian nephron, aldosterone promotes reabsorption of sodium by the principal cells of the cortical portion of the collecting duct. This results from hormone-induced increase in conductance for sodium at the apical role of the target cells, and later on, from associated increased density of the sodium "pump" units at the basolateral pole. Studies carried out on amphibian epithelia indicate that chloride permeability-of mitochondria-rich cells, and in all likelihood--is concurrently increased by aldosterone. It therefore looks as though this steroid hormone influences in a concerted way two cell populations, one being involved in transepithelial sodium transport, the other one representing the route of passage for the accompanying anion.
Bull Mem Acad R Med Belg 1989
PMID:[Mechanism of action of aldosterone as a regulatory factor of the extracellular volume]. 280 78

Epithelial ion transport in various organs has long been known to be controlled by extracellular agonists acting via membrane receptors or by intracellular messengers. Evidence is mounting for regulation of transport by direct interaction among membrane proteins or between a membrane transport protein and membrane-attached proteins. The membrane protein CFTR (Cystic Fibrosis Transmembrane Regulator) is widely expressed along the length of the nephron, but its role as a chloride channel does not appear to be critical for renal handling of salt and water. It is well established that the inward rectifying K channels (ROMK = Kir 1.1) in the thick ascending limb of Henle and in principal cells of the collecting duct are inhibited by millimolar concentrations of cytosolic Mg-ATP. However, the mechanism of this inhibition has been an enigma. We propose that the ATP-Binding Cassette (ABC) protein CFTR is a cofactor for Kir 1.1 regulation. Indeed, Mg-ATP sensitivity of Kir 1.1 is completely absent in two different mouse models of cystic fibrosis. In addition, the open-closed state of CFTR appears to provide a molecular gating switch that prevents or facilitates the ATP sensing of Kir 1.1. Does Mg-ATP sensing by the CFTR- Kir 1.1 complex play a role in coupling metabolism to ion transport? Physiological intracellular ATP concentrations in tubule cells are in the millimolar range, a saturating concentration for the gating of Kir 1.1 by Mg-ATP. Therefore, Kir 1.1 channels would be closed and unable to contribute to regulation of potassium secretion unless some other process modulated the CFTR-dependent ATP-sensitivity of Kir 1.1. The third component of the metabolic sensor-effector complex for Kir 1.1 regulation is most likely the AMP-regulated serine-threonine kinase, AMP kinase (AMPK). Changing levels in AMP rather than in ATP constitute the metabolic signal "sensed" by tubule cells. Because AMPK inhibits CFTR by modulating CFTR channel gating, we propose that renal K secretion is physiologically regulated by tri-molecular interactions between Kir 1.1, CFTR and AMPK.
Bull Mem Acad R Med Belg 2009
PMID:Protein-protein interactions among ion channels regulate ion transport in the kidney. 2012 88