Neuropeptide Y shifts equilibrium between alpha- and beta-adrenergic tonus in proximal tubule cells.

Abstract

Renal sympathetic nerves play a central role in the regulation of tubular Na+ reabsorption. Norepinephrine (NE) and neuropeptide Y (NPY) are colocalized in renal sympathetic nerve endings. The purpose of this study is to examine the integrated effects of these neurotransmitters on the regulation of Na+-K+-ATPase, the enzyme responsible for active Na+ reabsorption in renal tubular cells. Studies were performed on proximal tubular segments, which express adrenergic alpha- and beta-receptors, as well as NPY-Y2 receptors. It was found that alpha- and beta-adrenergic agonists had opposing effects on Na+-K+-ATPase activity. beta-Adrenergic agonists induced a dose-dependent inhibition of the Na+-K+-ATPase activity, whereas alpha-adrenergic agonists stimulated the enzyme. NPY abolished beta-agonist-induced deactivation of Na+-K+-ATPase and enhanced alpha-agonist-induced activation of Na+-K+-ATPase. The beta-adrenergic agonist appeared to inhibit Na+-K+-ATPase activity via a cAMP pathway. NPY antagonized beta-agonist-induced accumulation of cAMP. In our preparation, NE alone had no net effect but stimulated the Na+-K+-ATPase activity in the presence of beta-adrenergic antagonists, as well as in the presence of NPY. The results indicate that, in renal tissue, NPY determines the net effect of its colocalized transmitter, NE, by its ability to attenuate the beta- and enhance the alpha-adrenergic effect.