Wright E M, Wright S H, Hirayama B, Kippen I
Proc Natl Acad Sci U S A. 1982 Dec;79(23):7514-7. doi: 10.1073/pnas.79.23.7514.
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.
在从兔肾皮质分离出的刷状缘膜囊泡中研究了锂对三羧酸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转运穿过肾刷状缘膜。当添加到摄取培养基中时，锂作为琥珀酸/钠共转运的强效、特异性竞争性抑制剂（Ki = 1.2 mM）。对柠檬酸观察到类似的效果，但对D-葡萄糖、L-苯丙氨酸、L-脯氨酸、L-丙氨酸或L-乳酸的转运没有影响。在没有钠的情况下，囊泡内的锂表现为琥珀酸转运的非竞争性抑制剂。这些结果解释了治疗剂量的锂会增加三羧酸循环中间产物肾排泄这一观察结果。突触体中存在α-酮戊二酸转运系统表明锂在中枢神经系统中可能有作用靶点。
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