2-Aminoethyl diphenylborinate analogues: Selective inhibition for store-operated Ca²⁺ entry

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• 作者：Hong Zhou ; Hirohide Iwasaki ; Takeshi Nakamura ; Kyoko Nakamura ; Takayuki Maruyama ; Shin-ichi Hamano ; Shoichiro Ozaki ; Akihiro Mizutani ; Katsuhiko Mikoshiba
• 关键词：CCE ; SOC ; IICR ; 2APB ; Icrac ; IP3R ; TRP ; STIM1 ; Orai1 ; Inhibitor
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2007
• 出版时间：12 January 2007
• 年：2007
• 卷：352
• 期：2
• 页码：277-282
• 全文大小：202 K

文摘

Capacitative calcium entry (CCE), the mechanism that replenishes the internal Ca²⁺ stores with Ca²⁺ from the extracellular milieu in response to depletion of the store, is mediated by Ca²⁺ channels in the plasma membrane generally referred to as store-operated channels (SOCs). However, the roles of SOCs in the more physiological context have been fully elucidated. 2-Aminoethyl diphenylborinate (2-APB) strongly inhibits SOCs, as well as inositol-1,4,5 trisphosphate (IP₃) receptors. In the present study, we screened a library of 166 2-APB analogues for effects on CCE and IP₃-induced Ca²⁺ release in order to discover specific SOC inhibitors, and found that some blocked both store-operated and receptor-operated Ca²⁺ influx more strongly and selectively than 2-APB. Indeed, these new compounds ceased the prolonged intracellular Ca²⁺ oscillations induced by a low concentration of ATP in CHO-K1 cells. These novel SOC inhibitors will be valuable pharmacological and biochemical tools for elucidating the physiological roles.