Functional Proteins Involved in Regulation of Intracellular Ca2+ for Drug Development:Pharmacology of SEA0400, a Specific Inhibitor of the Na+-Ca2+ Exchanger

Journal of Pharmacological Sciences

Akemichi Baba¹  Yutaka Koyama²  Toshio Matsuda² 

[1] Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University;Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University

关键词: Na+-Ca2+ exchanger;    SEA0400;    edema;    ischemia/reperfusion injury;    apoptosis;   

DOI  :  10.1254/jphs.FMJ04007X2

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(38)Cited-By(12)The Na+-Ca2+ exchanger (NCX) is involved in regulation of intracellular Ca2+ concentration. A specific inhibitor of NCX has been required for clarification of the physiological and pathological roles of NCX. We have developed 2-[4-[(2,5-difluorophenyl)methoxy]phenoxy]-5-ethoxyaniline (SEA0400), a highly potent and selective inhibitor of NCX. SEA0400 in the concentration range that inhibits NCX exhibits negligible affinities for the Ca2+ channels, Na+ channels, K+ channels, noradrenaline transporter, and 14 receptors; and it does not affect the activities of the store-operated Ca2+ channel, Na+-H+ exchanger, and several enzymes including Na+,K+-ATPase and Ca2+-ATPase. Furthermore, recent studies show that SEA0400 attenuates ischemia-reperfusion injury in the brain, heart, and kidney and radiofrequency lesion-induced edema in rat brain. These findings suggest that NCX plays a key role in ischemia-reperfusion injury and may be a target molecule for treatment of reperfusion injury-related diseases.

【 授权许可】

Unknown