Atrial natriuretic peptides and urodilatin modulate proximal tubule Na(+)-ATPase activity through activation of the NPR-A/cGMP/PKG pathway.
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.
Vives
Diogo
D
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, CCS-bloco G, 21941-902 Rio de Janeiro, RJ, Brazil.
Farage
Sílvia
S
Motta
Rafael
R
Lopes
Anibal G
AG
Caruso-Neves
Celso
C
D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D027682:Cation Transport Proteins / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D015151:Immunoblotting; D007687:Kidney Tubules, Proximal / Q000201:enzymology*; D010446:Peptide Fragments / Q000494:pharmacology; D017461:Receptors, Atrial Natriuretic Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013552:Swine
D027682:Cation Transport Proteins; D010446:Peptide Fragments; C056452:Ularitide; D009320:Atrial Natriuretic Factor; D017869:Cyclic GMP-Dependent Protein Kinases; D000251:Adenosine Triphosphatases; C021838:sodium-translocating ATPase; D017461:Receptors, Atrial Natriuretic Factor; D006152:Cyclic GMP