Hormonal regulation of the Na(+)-K(+)-ATPase: mechanisms underlying rapid and sustained changes in pump activity

The sodium-potassium-activated adenosinetriphosphatase (Na(+)-K(+)-ATPase; Na(+)-K+ pump) is a ubiquitous plasma membrane enzyme that catalyzes the movement of K+ into cells in exchange for Na+. In addition, it provides the driving force for the transport of other solutes, notably amino acids, sugar, and phosphate. The regulation of Na(+)-K(+)-ATPase in various tissues is under the control of a number of circulating hormones that impart both short- and long-term control over its activity. The molecular mechanisms by which hormones alter Na(+)-K(+)-ATPase activity have only begun to be studied. In this review, we assess the acute and long-term actions of a number of hormones (aldosterone, thyroid hormone, catecholamines, insulin, carbachol) on the Na(+)-K+ pump. The long-term regulation exerted by thyroid hormone and aldosterone is mediated by changes in gene expression. The short-term regulation exerted by catecholamines is mediated by reversible phosphorylation of the pump catalytic subunit. Recent evidence supports regulation of the pump by phosphorylation in vitro and in intact cells. Finally, in some tissues the rapid action of insulin, aldosterone, and carbachol involves changes in the subcellular distribution of pump units.