Effect of indomethacin in vivo and PGE2 in vitro on MTAL Na-K-ATPase of the rat kidney

Abstract

We have previously shown that prostaglandin synthesis inhibition in rats which reduces urinary excretion of PGE2 and sodium, is associated with increased Na-K-ATPase activity in renal medulla. To further characterize this interaction studies were performed in isolated segments of medullary thick ascending limb of Henle's loop (MTAL) in rats. The effect of pretreatment with indomethacin in vivo and incubation with PGE2 in vitro on MTAL Na-K-ATPase activity was studied. Pretreatment of rats with indomethacin increased Na-K-ATPase of the MTAL from 37.2 +/- 2.0 x 10(-11) mol/mm/min in controls to 62.7 +/- 2.2 (p less than 0.001) while Mg-ATPase was only slightly decreased. Incubation of MTAL Na-K-ATPase from indomethacin pretreated rats with increasing concentration of PGE2 in vitro dose dependently inhibited MTAL Na-K-ATPase activity with no effect on Mg-ATPase. Baseline Na-K-ATPase was 62.7 +/- 2.2 in MTAL from indomethacin pretreated rats and decreased to 36.9 +/- 1.4 (p less than 0.001) with 1 microM of PGE2, to 26.5 +/- 2.3 (p less than 0.001) with 10 microM PGE2 and to 22.0 +/- 1.0 (p less than 0.001) with 100 microM PGE2. 100 microM PGE2 in the incubation medium inhibited MTAL Na-K-ATPase of intact rats from 37.2 +/- 2 to 21.3 +/- 1.2 (p less than 0.001) and completely abolished the indomethacin induced increase in MTAL Na-K-ATPase. The results of this study show stimulation of MTAL Na-K-ATPase by pretreatment with indomethacin in vivo and, direct inhibition of MTAL Na-K-ATPase by PGE2 in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)