Carroll M A, Louzan M, McGiff J C
Department of Pharmacology, New York Medical College, Valhalla 10595.
Am J Physiol. 1990 Apr;258(4 Pt 2):F1084-9. doi: 10.1152/ajprenal.1990.258.4.F1084.
We studied the effects of K+ on cytochrome P-450-dependent arachidonic acid (P450-AA) metabolism by cells isolated from the rabbit medullary thick ascending limb of Henle's loop (MTAL) by varying K+ from 0 to 7.5 mM in the incubating medium because of the known effects of K+ on AA metabolism. Rabbit MTAL cells convert AA to metabolites that segregate into two peaks (P1 and P2) on reverse-phase high-performance liquid chromatography; P1 contains vasodilator material and P2 an inhibitor(s) of Na(+)-K(+)-ATPase activity. Formation of P450-AA metabolites by MTAL was enhanced by reducing external K+ (P less than 0.01) and was not affected by changes in external Cl- but was dependent on the presence of intact MTAL cells, suggesting that P450-AA metabolism was related to altering ion fluxes and/or cell volume changes. The effects of altered external K+ on MTAL P450-AA metabolism could be nullified by increasing K+ intake before killing the rabbits. Evidence for the absence of a direct effect of zero K+ on Na(+)-K(+)-ATPase was provided by the demonstration that ouabain failed to affect AA metabolism in MTAL cells. We conclude that P450-AA metabolism by MTAL cells can be influenced either directly by altering external K+ in the incubate or indirectly by changing dietary K+ before killing the rabbits. Furthermore, MTAL P450-AA metabolism was independent of changes in external Cl- and Na(+)-K(+)-ATPase activity.
由于已知钾离子对花生四烯酸（AA）代谢有影响，我们通过在孵育培养基中将钾离子浓度从0变化到7.5 mM，研究了钾离子对从兔髓袢升支粗段（MTAL）分离的细胞中细胞色素P-450依赖的花生四烯酸（P450-AA）代谢的影响。兔MTAL细胞将AA转化为代谢产物，这些代谢产物在反相高效液相色谱上分离为两个峰（P1和P2）；P1含有血管舒张物质，P2含有Na(+)-K(+)-ATP酶活性抑制剂。降低细胞外钾离子可增强MTAL中P450-AA代谢产物的形成（P<0.01），且不受细胞外氯离子变化的影响，但依赖于完整MTAL细胞的存在，这表明P450-AA代谢与改变离子通量和/或细胞体积变化有关。在处死兔子前增加钾离子摄入量可消除细胞外钾离子改变对MTAL P450-AA代谢的影响。哇巴因未能影响MTAL细胞中AA代谢，这证明了零钾离子对Na(+)-K(+)-ATP酶无直接作用。我们得出结论，MTAL细胞的P450-AA代谢可通过改变孵育液中的细胞外钾离子直接影响，或通过在处死兔子前改变饮食中的钾离子间接影响。此外，MTAL的P450-AA代谢与细胞外氯离子和Na(+)-K(+)-ATP酶活性的变化无关。
