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Inhibitory Mechanism of SN‐6, A Novel Benzyloxyphenyl Na + /Ca 2+ Exchange Inhibitor
Author(s) -
KITA SATOMI,
IWAMOTO TAKAHIRO
Publication year - 2007
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1387.040
Subject(s) - chemistry , sodium calcium exchanger , transfection , biophysics , efflux , inhibitory postsynaptic potential , microbiology and biotechnology , stereochemistry , intracellular , biochemistry , gene , biology , endocrinology
We investigated the pharmacological properties of SN‐6, a new selective Na + /Ca 2+ exchanger (NCX) inhibitor. SN‐6 preferentially inhibited the 45 Ca 2+ uptake via NCX compared with the 45 Ca 2+ efflux via NCX in NCX‐transfected fibroblasts. SN‐6 was three‐ to fivefold more inhibitory to the 45 Ca 2+ uptake via NCX1 (IC 50 = 2.9 μM) than to that via NCX2 or NCX3. Our chimeric and site‐directed mutageneses 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.