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

Biochem Biophys Res Commun. 2007 Jan 12;352(2):277-82. doi: 10.1016/j.bbrc.2006.10.174. Epub 2006 Nov 7.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Boron Compounds / administration & dosage*
  • CHO Cells
  • Calcium / metabolism*
  • Calcium Channels / drug effects*
  • Calcium Channels / physiology
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism*
  • Cricetinae
  • Cricetulus
  • Ion Channel Gating / drug effects
  • Ion Channel Gating / physiology*
  • Metabolic Clearance Rate / drug effects

Substances

  • Boron Compounds
  • Calcium Channels
  • 2-aminoethoxydiphenyl borate
  • Calcium