Selective inhibition of calcium influx by 2-aminoethoxydiphenyl borate

Abstract

2-aminoethoxydiphenyl borate (2APB) blocks agonist-induced Ca 2+ mobilization from intracellular stores and Ca 2+ entry. To compare the sensitivity profiles of these two components of calcium signaling, human platelets were exposed to different concentrations of 2APB. The drug interferes with the Ca 2+ mobilization from intracellular stores induced by thrombin with an IC 50 of 52 ± 2 μM but it has a more potent inhibitory effect on the Ca 2+ entry (IC 50 = 16 ± 1 μM). This value was similar to the IC 50 found when the immediate inhibition of the calcium entry was studied after Ca 2+ mobilization was completed (IC 50 = 18 ± 5 μM). The calcium influx induced by thapsigargin showed an IC 50 of 17 ± 1 μM for the immediate inhibition. The sensitivity to bivalent ion entry to 2APB was confirmed by Mn 2+ entry inhibition. Although the specificity of 2APB with respect to the intracellular signaling system has not been fully established, our results confirm that the direct inhibition of calcium entry through the store-operated channels requires lower concentrations than the inhibition of mobilization, suggesting an independent and different site of action.