ADP INDUCES INOSITOL PHOSPHATE-INDEPENDENT INTRACELLULAR CA2-CELLS( MOBILIZATION IN BRAIN CAPILLARY ENDOTHELIAL)

The action of adenine and uracyl nucleotides on rat brain capillary en dothelial cells was investigated. ATP, UTP, and adenosine 5'-O-(3-thio trisphosphate) activated phospholipase C and induced large increases i n [Ca2+]i. ADP had a different action. At low concentrations (<10 muM) , ADP induced the mobilization of a thapsigargin-sensitive intracellul ar Ca2+ store in the absence of measurable production of inositol phos phates. At larger concentrations (>30 mum), ADP activated phospholipas e C. The actions of ATP and ADP and of UTP and ADP were additive. Thos e of ATP and UTP were not. In the presence of ATP or UTP, the dose-res ponse 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-de sensitization of the actions of ATP and UTP were observed. It is concl uded that two types of receptors account for the actions of nucleotide s: (i) a nucleotide that recognizes ATP and UTP and that is positively coupled to phospholipase C; and (ii) an ADP-specific receptor that in duces the mobilization of a thapsigargin-sensitive intracellular Ca2pool in a manner independent of the formation of inositol phosphates.