Kita Satomi, Iwamoto Takahiro
Department of Pharmacology, School of Medicine, Fukuoka University, Fukuoka 814-0180, Japan.
Ann N Y Acad Sci. 2007 Mar;1099:529-33. doi: 10.1196/annals.1387.040.
We investigated the pharmacological properties of SN-6, a new selective Na+/Ca2+ exchanger (NCX) inhibitor. SN-6 preferentially inhibited the (45)Ca2+ uptake via NCX compared with the (45)Ca2+ efflux via NCX in NCX-transfected fibroblasts. SN-6 was three- to fivefold more inhibitory to the (45)Ca2+ uptake via NCX1 (IC50 = 2.9 microM) than to that via NCX2 or NCX3. Our chimeric and site-directed mutagenesis revealed that Phe-213, Val-227, Tyr-228, Gly-833, and Asn-839 in NCX1 are molecular determinants for interaction with SN-6. We also found that SN-6 potently protects against hypoxia/reoxygenation-induced cell damage in renal tubular cells.
我们研究了新型选择性钠/钙交换体（NCX）抑制剂SN-6的药理特性。与经NCX转染的成纤维细胞中通过NCX的（45）Ca2+外流相比，SN-6优先抑制通过NCX的（45）Ca2+摄取。SN-6对通过NCX1的（45）Ca2+摄取（IC50 = 2.9 microM）的抑制作用比对通过NCX2或NCX3的抑制作用强三至五倍。我们的嵌合和定点诱变研究表明，NCX1中的苯丙氨酸-213、缬氨酸-227、酪氨酸-228、甘氨酸-833和天冬酰胺-839是与SN-6相互作用的分子决定因素。我们还发现，SN-6能有效保护肾小管细胞免受缺氧/复氧诱导的细胞损伤。
