Characterization of the effects of 2‐methylthio‐ATP and 2‐chloro‐ATP on brain capillary endothelial cells: similarities to ADP and differences from ATP

1 Brain capillary endothelial cells responded to 2‐methylthio‐ATP (2MeSATP) by large increases in [Ca2+]i (EC50 = 27 nm) that were partially dependent on the presence of extracellular Ca2+ and that were not associated with a measurable production of inositol phosphates. 2 2‐chloro‐ATP (2ClATP) raised [Ca2+]i in a biphasic manner. At low concentrations, intracellular Ca2+ mobilization was not associated with a measurable production of inositol phosphates. At concentrations >30 μm, 2ClATP activated phospholipase C. 3 The actions of 2ClATP, 2MeSATP and ADP on [Ca2+]i were additive to those of ATP and UTP. Non‐additive actions of 2MeSATP and of low concentrations of ADP or of 2ClATP were observed. 4 Cross desensitizations of the actions of ADP, 2MeSATP and 2ClATP were observed. None of them desensitized cells to the action of ATP. 5 It is concluded that 2MeSATP and low concentrations of 2ClATP and ADP induce intracellular Ca2+ mobilization by acting via an atypical P2y purinoceptor that is not coupled to phospholipase C. At high concentrations, 2C1ATP also activates phospholipase C and further increases [Ca2+]i probably by acting on P2u purinoceptors.