Bradykinin modulates the ouabain-insensitive Na+-ATPase activity from basolateral membrane of the proximal tubule

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 B-2 receptor, Hyp(3), 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 Hyp(3), 10(-10) M bradykinin stimulated the Na+-ATPase activity by 45% in the basolateral membrane preparations. The increase in des-Arg(9)-bradykinin concentration from 10(-12) to 10(-7) M, an agonist of the B-1 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 mu M 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 B-1 receptors and inhibited the enzyme through the interaction with B-2 receptors. Furthermore, the cortex homogenate expresses a kininase T activity that cleaves bradykinin to des-Arg(9)-bradykinin. (C) 1999 Elsevier Science B.V. All rights reserved.