Evidence That Binding of Cyclic GMP to the Extracellular Domain of Na+/K+-ATPase Mediates Natriuresis

Schematic diagram of cyclic GMP-dependent signaling pathways in the renal proximal tubule cell leading to reduced sodium (Na + ) transport and natriuresis in response to increased renal perfusion pressure. Increased renal perfusion pressure increases cGMP production in renal proximal tubule cells. I...

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Bibliographic Details
Published in:Circulation research 2023-03, Vol.132 (9), p.1127-1140
Main Authors: Kemp, Brandon A., Howell, Nancy L., Gildea, John J., Hinkle, Josh D., Shabanowitz, Jeffrey, Hunt, Donald F., Conaway, Mark R., Keller, Susanna R., Carey, Robert M.
Format: Article
Language:English
Online Access:Get full text
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Summary:Schematic diagram of cyclic GMP-dependent signaling pathways in the renal proximal tubule cell leading to reduced sodium (Na + ) transport and natriuresis in response to increased renal perfusion pressure. Increased renal perfusion pressure increases cGMP production in renal proximal tubule cells. In a unidirectional process, cGMP is transported across the basolateral membrane by a probenecid-sensitive organic anion transporter into the renal interstitial fluid where it binds to the ouabain binding pocket on the extracellular domain of NKA. cGMP binding to NKA activates Src kinase resulting in internalization and inactivation of Na + transporters, NHE-3 and NKA, and natriuresis. cGMP, cyclic 3’,5’-guanosine monophosphate; NHE-3, sodium-hydrogen exchanger-3; NKA, sodium-potassium-ATPase; NO, nitric oxide; NOS, soluble nitric oxide synthase; OAT, organic anion transporter; OUA, ouabain; sGC, soluble guanylyl cyclase; Src, Src-family kinase.
ISSN:0009-7330
1524-4571
DOI:10.1161/CIRCRESAHA.122.321693