Ouabain-insensitive Na+-ATPase of proximal tubules is an effector for urodilatin and atrial natriuretic peptide.
In the present paper we studied the effect of urodilatin and atrial natriuretic peptide (ANP) on the proximal tubule Na+-ATPase and (Na+K+)ATPase activities. Urodilatin and ANP inhibit the Na+-ATPase activity but not the (Na+K+)ATPase activity. Maximal effect was observed at a concentration of 10(-11) M for both peptides. In this condition, the enzyme activity decreases from 10.8 +/- 1.6 (control) to 5.7 +/- 0.9 or 6.1 +/- 0.7 nmol Pi mg(-1) min(-1) in the presence of urodilatin or ANP, respectively. This effect was completely reversed by 10(-6) M LY83583, a guanylyl cyclase inhibitor, and mimicked by 10 nM cGMP. Furthermore, both ANP and urodilatin increase cGMP production by 33% and 49%, respectively. This is the first demonstration that it was shown that urodilatin and ANP directly modulate primary active sodium transport in the proximal tubule. The data obtained indicate that this effect is mediated by the activation of the NPR-A/guanylate cyclase/cGMP pathway.
Caruso-Neves
C
C
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, CCS-Bloco G, 21949-900-Rio de Janeiro, RJ, Brazil.
Vives
D
D
Dantas
C
C
Albino
C M
CM
Fonseca
L M
LM
Lara
L S
LS
Iso
M
M
Lopes
A G
AG
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D027682:Cation Transport Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004848:Epithelium / Q000187:drug effects; D006162:Guanylate Cyclase / Q000378:metabolism; D007684:Kidney Tubules / Q000187:drug effects / Q000201:enzymology*; D010042:Ouabain / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D017461:Receptors, Atrial Natriuretic Factor / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013552:Swine
D027682:Cation Transport Proteins; D004791:Enzyme Inhibitors; D010446:Peptide Fragments; D010042:Ouabain; C056452:Ularitide; D009320:Atrial Natriuretic Factor; D012964:Sodium; D000251:Adenosine Triphosphatases; C021838:sodium-translocating ATPase; D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor; C091715:atrial natriuretic factor receptor A; D000254:Sodium-Potassium-Exchanging ATPase; D006152:Cyclic GMP