Soltoff S P, Cragoe E J, Mandel L J
Am J Physiol. 1986 May;250(5 Pt 1):C744-7. doi: 10.1152/ajpcell.1986.250.5.C744.
The effects of two amiloride analogues, ethylisopropylamiloride and methylisopropylamiloride, were tested on active Na+ transport and oxidative metabolism of a rabbit proximal renal tubule suspension. These two analogues have been recently reported to inhibit Na+-H+ antiport activity of various tissues with greater potency than amiloride. In proximal tubules, no effects were detected at concentrations less than 10(-4) M. At concentrations greater than 10(-4) M, both of these compounds inhibited the ouabain-sensitive O2 consumption (a direct measure of Na+ pump activity) with a greater potency than amiloride. Investigations into possible metabolic effects revealed that both amiloride analogues inhibited mitochondrial production of ATP at these concentrations, whereas amiloride did not directly affect metabolism. The amiloride analogues inhibited the nystatin-stimulated O2 consumption (which measures Na+-K+-ATPase activity in the intact cells) as well as the ATP content. These results suggest that the primary effects of these analogues on rabbit proximal tubules are to inhibit both the Na+-K+-ATPase and oxidative metabolism.
测试了两种氨氯地平类似物，即乙基异丙基氨氯地平和甲基异丙基氨氯地平，对兔近端肾小管悬浮液的活性钠转运和氧化代谢的影响。最近有报道称，这两种类似物比氨氯地平更有效地抑制各种组织的钠氢逆向转运活性。在近端小管中，浓度低于10^(-4) M时未检测到影响。浓度高于10^(-4) M时，这两种化合物均比氨氯地平更有效地抑制哇巴因敏感的氧消耗（钠泵活性的直接指标）。对可能的代谢影响的研究表明，在这些浓度下，两种氨氯地平类似物均抑制线粒体ATP的产生，而氨氯地平不直接影响代谢。氨氯地平类似物抑制制霉菌素刺激的氧消耗（测量完整细胞中的钠钾ATP酶活性）以及ATP含量。这些结果表明，这些类似物对兔近端小管的主要作用是抑制钠钾ATP酶和氧化代谢。
