The sodium pump and cardiotonic steroids-induced signal transduction protein kinases and calcium-signaling microdomain in regulation of transporter trafficking

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1802

Review

Liu, Jiang²  Xie, Zi-jian¹ 

[1] Univ Toledo, Coll Med, Dept Physiol & Pharmacol, Toledo, OH 43614 USA

[2] Univ Toledo, Coll Med, Dept Med, Toledo, OH 43614 USA

关键词: Na/K-ATPase;    Protein kinases;    Cardiotonic steroids;    Calcium signaling;    Renal sodium transporter;   

DOI  :  10.1016/j.bbadis.2010.01.013

来源: Elsevier

【 摘 要 】

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 Ca2+ 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. (c) 2010 Elsevier B.V. All rights reserved.

【 授权许可】

Free