Jabs K, Zeidel M L, Silva P
Department of Medicine, Children's Hospital, Boston, Massachusetts.
Am J Physiol. 1989 Sep;257(3 Pt 2):F424-30. doi: 10.1152/ajprenal.1989.257.3.F424.
Prostaglandin E2 (PGE2) is natriuretic and inhibits collecting duct sodium transport by poorly defined mechanisms. To determine the mechanism of this inhibition, we have studied the effect of PGE2 on ouabain-sensitive (transport-dependent) oxygen consumption (QO2), ouabain-sensitive 86Rb+ uptake and ouabain-sensitive ATPase activity in fresh suspensions of rabbit inner medullary collecting duct cells, as well as Na+-K+-ATPase activity in inner medullary membranes. PGE2 (10(-5) M) reduced total QO2 by 21.6 +/- 2.3% (mean +/- SE) and reduced the ouabain-sensitive component of QO2 in IMCD cells. PGE2 failed to inhibit QO2 in the absence of sodium or in the presence of ouabain and blunted the increase in QO2 in response to amphotericin B. These results suggested that PGE2 inhibited Na+-K+-ATPase activity. Inhibition of pump activity was confirmed by measurements of 86Rb+ uptake: PGE2 (10(-5) M) reduced ouabain-sensitive 86Rb+ uptake by 57% at 10 s without altering equilibrium uptake. Furthermore, PGE2 (10(-6) M) reduced ouabain-sensitive ATPase activity by 46% in permeabilized inner medullary collecting duct cells. PGF2 alpha (10(-5) M) did not significantly alter QO2, 86Rb+ uptake, or Na+-K+-ATPase activity. These results demonstrate that PGE2 inhibits inner medullary collecting duct Na+-K+-ATPase activity and suggest a role for this inhibition in the natriuretic effect of PGE2.
前列腺素E2（PGE2）具有利钠作用，并通过尚不明确的机制抑制集合管钠转运。为了确定这种抑制作用的机制，我们研究了PGE2对兔肾内髓集合管细胞新鲜悬浮液中哇巴因敏感（转运依赖性）耗氧量（QO2）、哇巴因敏感的86Rb+摄取以及哇巴因敏感的ATP酶活性的影响，以及对肾内髓膜中Na+-K+-ATP酶活性的影响。PGE2（10^(-5) M）使总QO2降低了21.6±2.3%（平均值±标准误），并降低了IMCD细胞中QO2的哇巴因敏感成分。在无钠或存在哇巴因的情况下，PGE2未能抑制QO2，并且减弱了对两性霉素B反应时QO2的增加。这些结果表明PGE2抑制了Na+-K+-ATP酶活性。通过测量86Rb+摄取证实了泵活性的抑制：PGE2（10^(-5) M）在10秒时使哇巴因敏感的86Rb+摄取降低了57%，而不改变平衡摄取。此外，PGE2（10^(-6) M）使透化的肾内髓集合管细胞中哇巴因敏感的ATP酶活性降低了46%。前列腺素F2α（10^(-5) M）未显著改变QO2、86Rb+摄取或Na+-K+-ATP酶活性。这些结果表明，PGE2抑制肾内髓集合管Na+-K+-ATP酶活性，并提示这种抑制作用在PGE2的利钠效应中发挥作用。
