2-Aminoethoxydiphenyl borate (2-APB) inhibits capacitative calcium entry independently of the function of inositol 1,4.5-trisphosphate receptors

H. Iwasaki, Y. Mori, Y. Hara, K. Uchida, H. Zhou, K. Mikoshiba

研究成果: Article

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Capacitative calcium entry (CCE), the mechanism that replenishes intracellular calcium stores after depletion, is essential to intracellular calcium signaling. CCE is mediated by the channels in the plasma membrane generally referred to as "store operated channels (SOCs)". However, the molecular identity of the SOCs has never been determined, and the mechanism of the activation of SOCs remains to be elucidated. Recent studies have demonstrated that 2-aminoethoxydiphenyl borate (2-APB), which has been found to be an antagonist of inositol 1,4,5-trisphosphate receptors (IP3Rs), inhibits CCE, suggesting that IP3Rs channel activity is essential to the generation of CCE. However, CCE has also been reported to occur normally in IP3R-deficient cells. In order to resolve this discrepancy, we investigated the effect of 2-APB on CCE in IP3Rs-deficient cells. In response to store depletion with thapsigargin or N,N,N',N'-tetrakis (2-pyridylmethyl) ethylene diamine (TPEN), CCE was generated in IP3Rs-deficient cells the same as in wild-type cells, however, 2-APB abolished CCE in IP3Rs-deficient cells, despite the fact that this cell line does not possess functional IP3Rs. We also examined the effect of 2-APB on several types of TRP Ca2+ channels, which exhibit properties similar to those of SOCs. 2-APB had a different inhibitory effect on spontaneous and thapsigargin-induced Ba2+ influx in cells that transiently expressed individual TRP subtypes. These results suggest that the channel activity of IP3Rs is not essential to the generation of CCE in this cell line and that 2-APB inhibits CCE independently of the function of IP3Rs.

元の言語English
ページ(範囲)429-439
ページ数11
ジャーナルReceptors and Channels
7
発行部数6
出版物ステータスPublished - 2001 12 1
外部発表Yes

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ASJC Scopus subject areas

  • Pharmacology
  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology

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