Angiotensin-(1-7) modulates the ouabain-insensitive Na+-ATPase activity from basolateral membrane of the proximal tubule.
Angiotensin-(1-7) (Ang-(1-7)) modulates the Na+-ATPase, but not the Na+,K+-ATPase activity present in pig kidney proximal tubules. The Na+-ATPase, insensitive to ouabain, but sensitive to furosemide, is stimulated by Ang-(1-7) (68% by 10(-9) M), in a dose-dependent manner. This effect is due to an increase in Vmax, while the apparent affinity of the enzyme for Na+ is not modified. Saralasin, a general angiotensin receptor antagonist, abolishes the stimulation, demonstrating that the Ang-(1-7) effect is mediated by receptor. The Ang-(1-7) stimulatory effect is not changed by either PD 123319, an AT2 receptor antagonist, or A779, an Ang-(1-7) receptor antagonist. On the other hand, increasing the concentration of the AT1 receptor antagonist losartan from 10(-11) to 10(-9) M, reverses the Ang(1-7) stimulation completely. A further increase to 10(-3) M losartan reverses the Na+-ATPase activity to a level similar to that obtained with Ang-(1-7) (10(-9) M) alone. The stimulatory effect of Ang-(1-7) at 10(-9) M is similar to the effect of angiotensin II (AG II) alone. However, when the two peptides are both present, Na+-ATPase activity is restored to control values. These data suggest that Ang-(1-7) selectively modulates the Na+-ATPase activity present in basolateral membranes of kidney proximal tubules through a losartan-sensitive receptor. This receptor is probably different from the receptor involved in the stimulation of the Na+-ATPase activity by angiotensin II.
Caruso-Neves
C
C
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brazil. caruso@ibccf.biof.ufrj.br
Lara
L S
LS
Rangel
L B
LB
Grossi
A L
AL
Lopes
A G
AG
D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000803:Angiotensin I / Q000494:pharmacology*; D000818:Animals; D027682:Cation Transport Proteins; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000201:enzymology; D009318:Natriuresis; D010042:Ouabain; D010446:Peptide Fragments / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology; D011945:Receptors, Angiotensin / Q000819:agonists; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013552:Swine
D027682:Cation Transport Proteins; D007093:Imidazoles; D010446:Peptide Fragments; D011725:Pyridines; D011945:Receptors, Angiotensin; C073402:PD 123319; D010042:Ouabain; D000803:Angiotensin I; D000251:Adenosine Triphosphatases; C021838:sodium-translocating ATPase; D000254:Sodium-Potassium-Exchanging ATPase; C118790:angiotensin I (1-7)