ADP induces inositol phosphate-independent intracellular Ca2+ mobilization in brain capillary endothelial cells

Abstract

The action of adenine and uracyl nucleotides on rat brain capillary endothelial cells was investigated. ATP, UTP, and adenosine 5'-O-(3-thiotrisphosphate) activated phospholipase C and induced large increases in [Ca2+]i. ADP had a different action. At low concentrations (< 10 microM), ADP induced the mobilization of a thapsigargin-sensitive intracellular Ca2+ store in the absence of measurable production of inositol phosphates. At larger concentrations (> 30 microM), ADP activated phospholipase C. The actions of ATP and ADP and of UTP and ADP were additive. Those of ATP and UTP were not. In the presence of ATP or UTP, the dose-response curve for ADP action on [Ca2+]i was monophasic and corresponded to the high affinity responses. Finally, we observed that ADP did not desensitize cells to the actions of ATP and UTP. In contrast, cross-desensitization of the actions of ATP and UTP were observed. It is concluded that two types of receptors account for the actions of nucleotides: (i) a nucleotide that recognizes ATP and UTP and that is positively coupled to phospholipase C; and (ii) an ADP-specific receptor that induces the mobilization of a thapsigargin-sensitive intracellular Ca2+ pool in a manner independent of the formation of inositol phosphates.