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) (EC(50) = 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 (2C1ATP) 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 mu M, 2C1ATP activated phospholipase C. 3 The actions of 2C1ATP, 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 2C1ATP were observed. 4 Cross desensitizations of the actions of ADP, 2MeSATP and 2C1ATP were observed. None of them desensitized cells to the action of ATP. 5 It is concluded that 2MeSATP and low concentrations of 2C1ATP and ADP induce intracellular Ca2+ mobilization by acting via an atypical P-2y 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 P-2u purinoceptors.