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 eit her by changing abundance of subunits, usually chronic processes, or b y altering existing transporters. Despite strong evidence from in vitr o observations, these mechanisms play an unclear role in the intact an imal. Particularly in the proximal nephron of the kidney, where the ra te of activity is high, in vivo regulation of the sodium pump is not w ell understood. In animal models of hypertension, Na,K-ATPase in the k idney displays an abnormal response to exogenous mineralocorticoid, in fused angiotensin II, or to application of catecholamines, suggesting the important influence of intracellular signaling pathways and recept ors. 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 ho rmonal regulation include direct and indirect effects on isoform trans cription, modification of isoform half-life, and posttranslational mod ification. Future investigation will clarify the precise molecular mec hanisms that occur at these intracellular sites.