TY - JOUR T1 - 2-Aminoethoxydiphenyl Borate Directly Inhibits Store-Operated Calcium Entry Channels in Human Platelets JF - Molecular Pharmacology JO - Mol Pharmacol SP - 541 LP - 552 VL - 60 IS - 3 AU - Yuliya Dobrydneva AU - Peter Blackmore Y1 - 2001/09/01 UR - http://molpharm.aspetjournals.org/content/60/3/541.abstract N2 - In this study, we examined 2-aminoethoxydiphenyl borate (2APB) as an inhibitor of Ca2+ influx in human platelets. 2APB was found to inhibit thrombin-mediated intracellular Ca2+mobilization rapidly in platelets incubated in the absence of extracellular Ca2+. This result supports an intracellular action of 2APB on inositol 1,4,5-trisphosphate (IP3)-receptor Ca2+ channels. 2APB was without effect on the ability of thapsigargin to mobilize intracellular Ca2+. This result suggests that the efflux of Ca2+ from the endoplasmic reticulum mediated by thapsigargin is not via IP3 Ca2+ channels. However, 2APB was able to prevent the entry of Ca2+ and Sr2+ through thapsigargin-activated, store-operated Ca2+ channels (SOCC). This result supports a direct inhibitory effect of 2APB on SOCC. 2APB was also able to block the entry of Sr2+, Ba2+, and Mn2+ entry into unstimulated platelets, which suggests that 2APB was inhibiting the Ca2+ influx channels directly. The capacity of 2APB to prevent Ca2+ influx and Sr2+ influx was rapid because it occurred immediately upon addition to the platelets. The inhibition of Ca2+ and Sr2+ influx by 2APB was similar to that seen with the cell-impermeable nonselective Ca2+-channel blocker La3+ or the Ca2+ chelator EGTA. Diphenylboronic anhydride and 2,2-diphenyltetrahydrofuran, two compounds that are structurally similar to 2APB, also inhibited Ca2+ influx. It was concluded that 2APB was a rapid and effective direct inhibitor of SOCC in human platelets; as such, it cannot be used to support the involvement of IP3 receptors in the activation of SOCC. The American Society for Pharmacology and Experimental Therapeutics ER -