title: Novel role of ouabain as a cystogenic factor in autosomal dominant polycystic kidney disease.
abstract: The classic role of the Na-K-ATPase is that of a primary active transporter that utilizes cell energy to establish and maintain transmembrane Na(+) and K(+) gradients to preserve cell osmotic stability, support cell excitability, and drive secondary active transport. Recent studies have revealed that Na-K-ATPase located within cholesterol-containing lipid rafts serves as a receptor for cardiotonic steroids, including ouabain. Traditionally, ouabain was viewed as a toxin produced only in plants, and it was used in relatively high concentrations to experimentally block the pumping action of the Na-K-ATPase. However, the new and unexpected role of the Na-K-ATPase as a signal transducer revealed a novel facet for ouabain in the regulation of a myriad of cell functions, including cell proliferation, hypertrophy, apoptosis, mobility, and metabolism. The seminal discovery that ouabain is endogenously produced in mammals and circulates in plasma has fueled the interest in this endogenous molecule as a potentially important hormone in normal physiology and disease. In this article, we review the role of the Na-K-ATPase as an ion transporter in the kidney, the experimental evidence for ouabain as a circulating hormone, the function of the Na-K-ATPase as a signal transducer that mediates ouabain's effects, and novel results for ouabain-induced Na-K-ATPase signaling in cystogenesis of autosomal dominant polycystic kidney disease.
authors.affiliation: Dept. of Molecular and Integrative Physiology, 3901 Rainbow Blvd., Kansas City, KS 66160. gblanco@kumc.edu.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Blanco
authors.forename: Darren P
authors.initials: DP
authors.lastname: Wallace
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000187:drug effects; D007684:Kidney Tubules / Q000502:physiology; D045283:Natriuretic Agents / Q000096:biosynthesis; D010042:Ouabain / Q000494:pharmacology*; D016891:Polycystic Kidney, Autosomal Dominant / Q000209:etiology / Q000503:physiopathology*; D015398:Signal Transduction / Q000187:drug effects; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects / Q000502:physiology*; D050396:TRPP Cation Channels / Q000235:genetics
chemical_list: D045283:Natriuretic Agents; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase; D050396:TRPP Cation Channels; C499076:ATP1A1 protein, human
keywords: Na-K-ATPase signalosome; cardiotonic steroids; polycystic kidney disease