Direct regulation of the Na,K pump by signal transduction mechanisms

There is clear precedent for a role of signal transduction pathways in modification of the renal sodium pump. Agonists regulate the pump either by changing abundance of subunits, usually chronic processes, or by altering existing transporters. Despite strong evidence from in vitro observations, these mechanisms play an unclear role in the intact animal. Particularly in the proximal nephron of the kidney, where the rate of activity is high, in vivo regulation of the sodium pump is not well understood. In animal models of hypertension, Na,K-ATPase in the kidney displays an abnormal response to exogenous mineralocorticoid, infused angiotensin II, or to application of catecholamines, suggesting the important influence of intracellular signaling pathways and receptors. It is not surprising that hormones and their receptors initiate a variety of discrete intracellular pathways to control activity of Na,K-ATPase. Intracellular sites that are documented to be employed in hormonal regulation include direct and indirect effects on isoform transcription, modification of isoform half-life, and posttranslational modification. Future investigation will clarify the precise molecular mechanisms that occur at these intracellular sites.