Interactions between lithium and renal transport of Krebs cycle intermediates.
Interactions between lithium and renal transport of Krebs cycle intermediates.
复制标题
锂与克雷布斯循环中间体的肾脏转运之间的相互作用。
DOI：
10.1073/pnas.79.23.7514
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发表时间：
1982
影响因子：
11.1
通讯作者：
Kippen,I
中科院分区：
文献类型：
--
作者：
Wright,EM;Wright,SH;Hirayama,B;Kippen,I
在离体兔肾皮质刷状缘膜囊泡中研究了锂对克雷布斯循环中间产物肾转运的影响。二羧酸和三羧酸通过钠共转运系统被积极地转运穿过肾刷状缘膜。锂作为一种有效的，具体的，竞争性抑制剂（Ki = 1.2 mM）的琥珀酸/钠共转运时，加入到摄取介质。对柠檬酸盐转运也观察到类似的作用，但对D-葡萄糖、L-苯丙氨酸、L-脯氨酸、L-丙氨酸或L-乳酸盐转运则没有观察到类似的作用。囊内锂表现为琥珀酸转运的非竞争性抑制剂，在钠的情况下。这些结果解释了治疗剂量的锂增加克雷布斯循环中间体的肾排泄的观察结果。突触体中α-酮戊二酸转运系统的存在表明锂在中枢神经系统中的可能靶点。
The effect of lithium on the renal transport of Krebs cycle intermediates was studied in brush border membrane vesicles isolated from the rabbit renal cortex. The di- and tricarboxylic acids are avidly transported across renal brush border membranes by a sodium cotransport system. Lithium acted as a potent, specific, competitive inhibitor (Ki = 1.2 mM) of succinate/sodium cotransport when added to the uptake medium. Similar effects were observed for citrate but not D-glucose, L-phenylalanine, L-proline, L-alanine, or L-lactate transport. Intravesicular lithium behaved as a noncompetitive inhibitor of succinate transport in the absence of sodium. These results account for the observation that therapeutic doses of lithium increase the renal excretion of Krebs cycle intermediates. The existence of a transport system for alpha-ketoglutarate in synaptosomes suggests a possible target for lithium in the central nervous system.