Selective inhibition of calcium influx by 2-aminoethoxydiphenyl borate.
2-aminoethoxydiphenyl borate (2APB) blocks agonist-induced Ca2+ mobilization from intracellular stores and Ca2+ 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 Ca2+ mobilization from intracellular stores induced by thrombin with an IC50 of 52+/-2 microM but it has a more potent inhibitory effect on the Ca2+ entry (IC50=16+/-1 microM). This value was similar to the IC50 found when the immediate inhibition of the calcium entry was studied after Ca2+ mobilization was completed (IC50=18+/-5 microM). The calcium influx induced by thapsigargin showed an IC50 of 17+/-1 microM for the immediate inhibition. The sensitivity to bivalent ion entry to 2APB was confirmed by Mn2+ 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.
Giambelluca
Miriam S
MS
Centro de Investigaciones Cardiovasculares, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, La Plata, Argentina.
Gende
Oscar A
OA
D001896:Boron Compounds / Q000494:pharmacology*; D002118:Calcium / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects; D006801:Humans; D017136:Ion Transport / Q000187:drug effects; D008345:Manganese / Q000378:metabolism; D019284:Thapsigargin / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology
D001896:Boron Compounds; D015220:Calcium Channels; D008345:Manganese; D019284:Thapsigargin; C109986:2-aminoethoxydiphenyl borate; D013917:Thrombin; D002118:Calcium