Saito H, Nishida H, Monma Y, Tanabe T
Jpn J Pharmacol. 1976 Apr;26(2):171-7. doi: 10.1254/jjp.26.171.
Experiments were undertaken to substantiate the hypothesis that the mechanism of the direct effect of ouabain on the renal excretion of electrolytes is the result of inhibition of the transport enzyme, (Na, K)-ATPase. In dogs hydrated with saline, an injection of 3H-ouabain into the unilateral renal artery produced a continuing marked increase in excretion of water and sodium from the kidney, but not from the counter kidney. At maximal diuresis--90 min after ouabain injection, both kidneys were removed to assay microsomal ATPase activity and determine radioactivity distributed in subcellular structures. It was demonstrated that 3H-ouabain was deposited in the microsome fraction obtained from the injected kidney in concentrations ranging from 10(-7) to 10(-6) M/kg wet weight, and (Na, K)-ATPase activity of this fraction was inhibited as compared with that of the microsomal fraction obtained from control kidneys. Since (Na, K)-ATPase activity of renal microsomes was significantly inhibited in vitro by more than 10(-7) M of ouabain, ouabain concentration in microsomes obtained from the injected kidney was considered to be sufficient to inhibit ATPase activity. These findings indicate that ouabain diuresis under the present condition is closely related to direct inhibitory effect of ouabain on (Na, K)-ATPase activity of microsomes in tubular cells.
哇巴因对肾电解质排泄的直接作用机制是由于转运酶（钠，钾）-ATP酶受到抑制。在用盐水水化的狗身上，向单侧肾动脉注射3H-哇巴因会使注射侧肾脏的水和钠排泄持续显著增加，而对侧肾脏则无此现象。在最大利尿时（哇巴因注射后90分钟），将双侧肾脏摘除以测定微粒体ATP酶活性并确定分布于亚细胞结构中的放射性。结果表明，从注射侧肾脏获得的微粒体部分中3H-哇巴因的沉积浓度为10（-7）至10（-6）M/千克湿重，与从对照肾脏获得的微粒体部分相比，该部分的（钠，钾）-ATP酶活性受到抑制。由于肾微粒体的（钠，钾）-ATP酶活性在体外被超过10（-7）M的哇巴因显著抑制，因此认为从注射侧肾脏获得的微粒体中的哇巴因浓度足以抑制ATP酶活性。这些发现表明，在当前条件下哇巴因利尿与哇巴因对肾小管细胞微粒体（钠，钾）-ATP酶活性的直接抑制作用密切相关。
