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 10314 to 10310 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 10310 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 10310 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 1037 M Hyp3, 10310 M bradykinin stimulated the Na -ATPase activity by 45% in the basolateral membrane preparations. The increase in des-Arg9-bradykinin concentration from 10312 to 1037 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 WM mergetpa, an inhibitor of kininase I, the increase in bradykinin concentration from 10312 to 10310 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 omogenate expresses a kininase I activity that cleaves bradykinin to des-Arg9-bradykinin. ß 1999 Elsevier Science B.V. All rights reserved.