Rates of synthesis and degradation of Na+-K+-ATPase during chronic ouabain treatment

Chronic inhibition of Na+-K+-ATPase activity in outer medullary kidney tubules has previously been demonstrated to elicit a 60% increase in activity, measured under maximal velocity (Vmax) conditions (J. Biol. Chem. 260: 12740-12743, 1985). To investigate the cellular mechanism of this response, we measured the rates of Na+-K+-ATPase synthesis and degradation over its full time course. A transient increase in the rate of synthesis occurred after 12 h of ouabain treatment. After 24-h treatment, the rate of synthesis returned to a level not different from control levels. The relative degradation rate after 24-h treatment, however, was markedly lower in ouabain-treated cells than in control cells. Thus the augmentation of the number of Na+-K+-ATPase sites, elicited by the transient increase in synthesis described, was maintained under steady-state conditions by a reduction in apparent degradation rate constant.