Summary-Interactions of the Na+-Ca2+ exchanger with small molecules on celt Ca2+ signaling were elucidated in Chinese hamster ovary (CHO) CI cells, which transfected a control vector without any expression of the Na*-Ca2+ exchanger's gene while CHO CK 1.4 cells transfected an expression vector encoding the bovine cardiac Na+-Caz+ exchanger's eDNA, treated with lithium or sodlum-buffer medRIm respectively, by using L16(2)15 muhifaetnrial orthogonal stallstics and fura-2 fluorescence real-time intaging In contrast to controls of Li*-treated Cl cells, [he store dependent CaZ+-influx (SDCI) was enhanced by either the Na*-Ca2+ exchanger, Na+, 1-β-3-(4-methoxyphenvl)propnxy1-4-methoxyphcnethyl}-IH-im daze e HC (SK&F96365 of nuahain. and by interactions of the Na*-Ca2+ exchanger with either Na" SK&F96365 or both SK&F96365 and ouabain; and ATP induced Ca2+. release (AICR) was activated by SK&F96365 or Na+ alone, interactions of the Na+-Ca2+ exchanger with SK&F96365 or Na+, and an interaetion between SK&F96365 and ouabain The dramatic interaction of the Na+-Ca2+ exchanger with small molecules indieates that cell Ca2+ signaling is generated by nositol triphnsphale (InsP3)-dependent pathways, allnsterie effects el the G protein coupled P2y&2u. purinoceptor and mnlti-sile recognition Our findings provide meaningful clues for designing new strategies of cardiocerebral vascular oxidative diseases