Bradykinin counteracts the stimulatory effect of angiotensin-(1-7) on the proximal tubule Na+ -ATPase activity through B2 receptor.
Recently, we demonstrated that angiotensin-(1-7) (Ang-(1-7)) stimulates the Na(+)-ATPase activity through a losartan-sensitive angiotensin receptor, whereas bradykinin inhibits the enzyme activity through the B(2) receptor [Regul. Pept. 91 (2000) 45; Pharmacol. Rev. 32 (1980) 1]. In the present paper, the effect of bradykinin (BK) on Ang-(1-7)-stimulated Na(+)-ATPase activity was evaluated. Preincubation of Na(+)-ATPase with 10(-9) M Ang-(1-7) increases enzyme activity from 7.9+/-0.9 to 14.1+/-1.5 nmol Pi mg(-1) min(-1), corresponding to an increase of 79% (p<0.05). This effect is reverted by bradykinin in a dose-dependent manner (10(-14)-10(-8) M), reaching maximal inhibitory effect at 10(-9) M. Des-Arg(9) bradykinin (DABK), an agonist of B(1) receptor, at the concentrations of 10(-9)-10(-7) M, does not mimic the BK inhibitory effect, and des-Arg(9)-[Leu(8)]-BK (DALBK), a B(1) receptor antagonist, at the concentrations of 10(-10)-10(-7) M, does not prevent the inhibitory effect of BK on Ang-(1-7)-stimulated enzyme. On the other hand, HOE 140, an antagonist of B(2) receptor, abolishes the inhibitory effect of BK on the Ang-(1-7)-stimulated enzyme in a dose-dependent manner, reaching maximal effect at 10(-7) M. Taken together, these data indicate that stimulation of B(2) receptors by BK can counteract the stimulatory effect of Ang-(1-7) on the proximal tubule Na(+)-ATPase activity.
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Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, CCS-Bloco G, 21949-900, Rio de Janeiro, RJ, Brazil.
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D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000803:Angiotensin I / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D000818:Animals; D001920:Bradykinin / Q000378:metabolism*; D065094:Bradykinin B2 Receptor Antagonists; D027682:Cation Transport Proteins / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000201:enzymology*; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D043782:Receptor, Bradykinin B2 / Q000378:metabolism*; D013552:Swine
D065094:Bradykinin B2 Receptor Antagonists; D027682:Cation Transport Proteins; D010446:Peptide Fragments; D043782:Receptor, Bradykinin B2; D000803:Angiotensin I; D000251:Adenosine Triphosphatases; C021838:sodium-translocating ATPase; C118790:angiotensin I (1-7); D001920:Bradykinin