Satoh T, Ominato M, Katz A I
First Department of Internal Medicine, St. Mariannna University School of Medicine, Kawasaki, Japan.
Hypertens Res. 1995 Jun;18 Suppl 1:S137-40. doi: 10.1291/hypres.18.supplementi_s137.
We reported a novel intracellular mechanism of renal Na-K-ATPase regulation by dopamine (DA) in the rat cortical collecting duct (CCD), which involves stimulation of protein kinase A (PKA) and phospholipase A2 (PLA2). In the present experiments we determined whether this mechanism also operates in other nephron segments. In the medullary thick ascending limbs (MTAL), DA and other cAMP agonists inhibited Na-K-ATPase activity, an effect that was abolished by PKA inhibitor IP20, but various protein kinase C (PKC) activators did not, analogous to our previous findings in CCD. In sharp contrast, DA inhibition on Na-K-ATPase in the proximal convoluted tubule (PCT) was reproduced by PKC agonists. These effects was blocked by PKC inhibitor staurosporine, but not by IP20. Mepacrine, a PLA2 inhibitor, reversed the pump effect of all agents, and arachidonic acid (AA) produced a dose-dependent pump inhibition, in all three nephron segments. We conclude that the intracellular mechanisms of Na-K-ATPase regulation by dopamine differ in the proximal and distal nephron, as they involve stimulation of PKA in MTAL and CCD, and of PKC in PCT. These two pathways probably share a common mechanism in stimulating PLA2 and AA release in both regions of the nephron.
我们报道了大鼠皮质集合管（CCD）中多巴胺（DA）对肾钠钾ATP酶调节的一种新的细胞内机制，该机制涉及蛋白激酶A（PKA）和磷脂酶A2（PLA2）的激活。在本实验中，我们确定了该机制是否也在其他肾单位节段发挥作用。在髓质厚升支（MTAL）中，DA和其他环磷酸腺苷（cAMP）激动剂抑制钠钾ATP酶活性，蛋白激酶A抑制剂IP20可消除该效应，但各种蛋白激酶C（PKC）激活剂则不能，这与我们之前在CCD中的发现类似。与之形成鲜明对比的是，PKC激动剂可重现DA对近端曲管（PCT）中钠钾ATP酶的抑制作用。这些效应可被PKC抑制剂星形孢菌素阻断，但不能被IP20阻断。磷脂酶A2抑制剂米帕林可逆转所有药物对泵的作用，花生四烯酸（AA）在所有三个肾单位节段均产生剂量依赖性的泵抑制作用。我们得出结论，多巴胺对钠钾ATP酶的细胞内调节机制在近端和远端肾单位有所不同，因为在MTAL和CCD中涉及PKA的激活，而在PCT中涉及PKC的激活。这两条途径可能在刺激肾单位两个区域的PLA2和AA释放方面具有共同机制。
