The sodium pump and cardiotonic steroids-induced signal transduction protein kinases and calcium-signaling microdomain in regulation of transporter trafficking.
The Na/K-ATPase was discovered as an energy transducing ion pump. A major difference between the Na/K-ATPase and other P-type ATPases is its ability to bind a group of chemicals called cardiotonic steroids (CTS). The plant-derived CTS such as digoxin are valuable drugs for the management of cardiac diseases, whereas ouabain and marinobufagenin (MBG) have been identified as a new class of endogenous hormones. Recent studies have demonstrated that the endogenous CTS are important regulators of renal Na(+) excretion and blood pressure. The Na/K-ATPase is not only an ion pump, but also an important receptor that can transduce the ligand-like effect of CTS on intracellular protein kinases and Ca(2+) signaling. Significantly, these CTS-provoked signaling events are capable of reducing the surface expression of apical NHE3 (Na/H exchanger isoform 3) and basolateral Na/K-ATPase in renal proximal tubular cells. These findings suggest that endogenous CTS may play an important role in regulation of tubular Na(+) excretion under physiological conditions; conversely, a defect at either the receptor level (Na/K-ATPase) or receptor-effector coupling would reduce the ability of renal proximal tubular cells to excrete Na(+), thus culminating/resulting in salt-sensitive hypertension.
Liu
Jiang
J
Department of Medicine, University of Toledo College of Medicine, Toledo, OH, USA.
Xie
Zi-Jian
ZJ
D000818:Animals; D002018:Bufanolides / Q000378:metabolism*; D020013:Calcium Signaling; D006801:Humans; D006973:Hypertension / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007687:Kidney Tubules, Proximal / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D010042:Ouabain / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism*; D021381:Protein Transport; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D002018:Bufanolides; C000613385:SLC9A3 protein, human; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; C093896:marinobufagenin; D010042:Ouabain; D011494:Protein Kinases; D000254:Sodium-Potassium-Exchanging ATPase