Regulation of the abundance of renal sodium transporters and channels by vasopressin.
Vasopressin plays a role in both salt and water balance in the kidney. Classic studies, utilizing isolated perfused tubules, have revealed that vasopressin increases sodium reabsorption in the kidney thick ascending limb and the collecting duct. Furthermore, the activity of several sodium transport proteins expressed in these segments, such as the bumetanide-sensitive Na-K-2Cl cotransporter (NKCC2) and the epithelial sodium channel (ENaC), have been shown to be directly increased by vasopressin. Increased protein abundance might be one means through which sodium transporter and channel activity is enhanced. We have used immunoblotting and immunohistochemistry in order to investigate the regulation of abundance of the major sodium transporters and channels expressed along the renal tubule in response to vasopressin. Chronic (7-day) studies were performed in which vasopressin levels were elevated either endogenously by water restriction of Sprague-Dawley rats or exogenously through infusion of the vasopressin V2-receptor-selective agonist, dDAVP (1-deamino-8d-arginine-vasopressin), to Brattleboro rats. We found a significant increase in protein abundance for NKCC2 and the beta- and gamma-subunits of ENaC with either water restriction or dDAVP infusion. The alpha-subunit of Na-K-ATPase was increased by water restriction, but not by dDAVP infusion, and alpha-ENaC and the thiazide-sensitive cotransporter (NCC) were increased by dDAVP infusion but not by water restriction. Acute (60-min) in vivo exposure to dDAVP led to an increase in both beta- and gamma-ENaC abundance in kidney cortex homogenates, displaying the rapid nature of some of these changes. Overall these increases in sodium transporter and channel abundances likely contribute to both the antidiuretic and antinatriuretic actions of vasopressin.
Ecelbarger
C A
CA
Division of Endocrinology and Metabolism, Georgetown University, Washington, DC 20007, USA.
Kim
G H
GH
Wade
J B
JB
Knepper
M A
MA
D000818:Animals; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology; D053503:Epithelial Sodium Channels; D006706:Homeostasis; D006801:Humans; D007668:Kidney / Q000502:physiology*; D021122:Protein Subunits; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology*; D028021:Sodium-Potassium-Chloride Symporters / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D064466:Solute Carrier Family 12, Member 1; D014882:Water-Electrolyte Balance
D053503:Epithelial Sodium Channels; D021122:Protein Subunits; C578714:SLC12A1 protein, human; C578716:Slc12a1 protein, rat; D015222:Sodium Channels; D028021:Sodium-Potassium-Chloride Symporters; D064466:Solute Carrier Family 12, Member 1; D000254:Sodium-Potassium-Exchanging ATPase; D003894:Deamino Arginine Vasopressin