Atrial natriuretic peptides and urodilatin modulate proximal tubule Na +-ATPase activity through activation of the NPR-A/cGMP/PKG pathway

• Published in: Peptides (New York, N.Y. : 1980) N.Y. : 1980), 2010-05, Vol.31 (5), p.903-908
• Main Authors: Vives, Diogo, Farage, Sílvia, Motta, Rafael, Lopes, Anibal G., Caruso-Neves, Celso
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphatases - metabolism; Animals; ANP and urodilatin; Atrial Natriuretic Factor - pharmacology; Biological and medical sciences; Cation Transport Proteins - metabolism; Cell Line; Cells, Cultured; Cyclic GMP - metabolism; Cyclic GMP-Dependent Protein Kinases - metabolism; Enzyme Activation - drug effects; Fundamental and applied biological sciences. Psychology; Immunoblotting; Kidney Tubules, Proximal - enzymology; Na +-ATPase; NPR-A; Peptide Fragments - pharmacology; Receptors, Atrial Natriuretic Factor - metabolism; Renal sodium excretion; Second sodium pump; Signal Transduction - drug effects; Swine; Vertebrates: endocrinology
• ISSN: 0196-9781; 1873-5169
• DOI: 10.1016/j.peptides.2010.02.018

The signaling pathway mediating modulation of Na +-ATPase of proximal tubule cells by atrial natriuretic peptides (ANP) and urodilatin through receptors located in luminal and basolateral membranes (BLM) is investigated. In isolated BLM, 10 −11 M ANP or 10 −11 M urodilatin inhibited the enzyme activity (50%). Immunodetection revealed the presence of NPR-A in BLM and LLC-PK1 cells. Both compounds increased protein kinase G (PKG) activity (80%) and this effect did not occur with 10 −6 M LY83583, a specific inhibitor of guanylyl cyclase. The inhibitory effect of these peptides on Na +-ATPase activity did not occur after addition of 10 −6 M KT5823, a specific inhibitor of PKG. LLC-PK1 cells were used to investigate if ANP and urodilatin change the activity of sodium pumps by luminal receptor interaction. ANP and urodilatin inhibited Na +-ATPase activity (50%), with maximal effect at 10 −10 M, similar to 10 −7 M db-cGMP, and did not occur with 10 −7 M LY83583, a guanylyl cyclase inhibitor. ANP and urodilatin specifically inhibit Na +-ATPase activity by activation of the cGMP/PKG pathway through NPR-A located in luminal membrane and BLM, increasing understanding of the mechanism of natriuretic peptides on renal sodium excretion, with proximal tubule Na +-ATPase one possible target.