CALCINEURIN MEDIATES ALPHA-ADRENERGIC STIMULATION OF NA+,K+-ATPASE ACTIVITY IN RENAL TUBULE CELLS

The alpha-adrenergic agonist oxymetazoline increased Na+,K+-ATPase activity of single proximal convoluted tubules dissected from rat kidney. Activation of the enzyme by oxymetazoline was prevented by either the alpha-1-adrenergic antagonist prazosin or the alpha-2-adrenergic antagonist yohimbine and was mimicked by the calcium ionophore A23187. The effect of oxymetazoline on Na+,K+-ATPase activity was prevented by a specific peptide inhibitor of calcineurin, as well as by FK 506, an immunosuppressant agent known to inhibit calcineurin; these results indicate that the action of oxymetazoline is mediated via activation of calcineurin (a calcium/calmodulin-dependent protein phosphatase). Activation of the Na+,K+-ATPase by either oxymetazoline or A23187 was associated with a > 2-fold increase in its affinity for Na+. The results provide a biochemical mechanism by which norepinephrine, released from renal nerve terminals, stimulates Na+ retention.