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 microM, 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, 2ClATP also activates phospholipase C and further increases [Ca2+]i probably by acting on P2u purinoceptors.