title: Bradykinin modulates the ouabain-insensitive Na+-ATPase activity from basolateral membrane of the proximal tubule.
abstract: This paper studies the modulation by bradykinin of the ouabain-insensitive Na+-ATPase activity in both renal cortex homogenate and basolateral membrane from proximal tubule. The increase in bradykinin concentration from 10-14 to 10-10 M stimulated the ouabain-insensitive Na+-ATPase activity in cortex homogenates about 2.2-fold, but inhibited the enzyme activity of basolateral membrane preparations by 60%. In both preparations, the maximal effect was obtained with 10-10 M bradykinin. Further increase in the concentration of bradykinin completely abolished these effects. The antagonist of the B2 receptor, Hyp3, completely abolished the effect of 10-10 M bradykinin on the Na+-ATPase activity in the basolateral membrane preparation in a dose-dependent manner, but had no effect on the bradykinin stimulated enzyme activity of the cortex homogenate. Furthermore, in the presence of 10-7 M Hyp3, 10-10 M bradykinin stimulated the Na+-ATPase activity by 45% in the basolateral membrane preparations. The increase in des-Arg9-bradykinin concentration from 10-12 to 10-7 M, an agonist of the B1 receptor, stimulated the Na+-ATPase activity of the cortex homogenates and of the basolateral membrane preparations by 105 and 148%, respectively. In the presence of 25 microM mergetpa, an inhibitor of kininase I, the increase in bradykinin concentration from 10-12 to 10-10 M promoted similar inhibition of the Na+-ATPase activity of both cortex homogenates and basolateral membrane preparations. These results suggest that bradykinin stimulated the Na+-ATPase activity of proximal tubule through the interaction with B1 receptors and inhibited the enzyme through the interaction with B2 receptors. Furthermore, the cortex homogenate expresses a kininase I activity that cleaves bradykinin to des-Arg9-bradykinin.
authors.affiliation: Instituto de Biofísica Carlos Chagas, Chagas Filho, Universidade Federal do Rio de Janeiro, CCS, Bloco G, 21949-900, Rio de Janeiro, RJ, Brazil.
authors.forename: C
authors.initials: C
authors.lastname: Caruso-Neves
authors.forename: A S
authors.initials: AS
authors.lastname: Siqueira
authors.forename: G
authors.initials: G
authors.lastname: Iso-Cohen
authors.forename: A G
authors.initials: AG
authors.lastname: Lopes
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D027682:Cation Transport Proteins; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D004789:Enzyme Activation / Q000187:drug effects; D007672:Kidney Cortex / Q000187:drug effects / Q000201:enzymology; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000201:enzymology; D001121:Lysine Carboxypeptidase; D010042:Ouabain; D007703:Peptidyl-Dipeptidase A; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000187:drug effects / Q000378:metabolism; D013552:Swine
chemical_list: D027682:Cation Transport Proteins; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; D010042:Ouabain; D007703:Peptidyl-Dipeptidase A; D001121:Lysine Carboxypeptidase; D000251:Adenosine Triphosphatases; C021838:sodium-translocating ATPase; D001920:Bradykinin