Atrial natriuretic peptides and urodilatin modulate proximal tubule Na super(+)-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, Silvia, Motta, Rafael, Lopes, Anibal G, Caruso-Neves, Celso
• Format: Article
• Language: English
• Subjects: Activation; Inhibitors; Kinases; Membranes; Pathways; Peptides; Receptors; Sodium
• ISSN: 0196-9781
• DOI: 10.1016/j.peptides.2010.02.018

The signaling pathway mediating modulation of Na super(+)-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 super(-11) M ANP or 10 super(-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 super(-6) M LY83583, a specific inhibitor of guanylyl cyclase. The inhibitory effect of these peptides on Na super(+)-ATPase activity did not occur after addition of 10 super(-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 super(+)-ATPase activity (50%), with maximal effect at 10 super(-10) M, similar to 10 super(-7) M db-cGMP, and did not occur with 10 super(-7) M LY83583, a guanylyl cyclase inhibitor. ANP and urodilatin specifically inhibit Na super(+)-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 super(+)-ATPase one possible target.