Mobilization of intracellular Ca2+ by adenine nucleotides in human T-leukaemia cells: evidence for ADP-specific and P2y-purinergic receptors.
The expression of purinergic receptors on human T-cells was investigated and the receptors were shown to be functionally coupled to intracellular signals in two out of eight T-leukaemia cell-lines. Addition of adenine nucleotides resulted in mobilization of intracellular Ca2+ in HPB-ALL cells and a cell line (CB1) recently isolated from a patient with T-acute lymphoblastic leukaemia. Of a range of nucleotides tested only ADP and ATP elevated intracellular levels of Ca2+, with ADP being the more potent agonist. Ca2+ mobilization by ATP was accompanied by increased inositol phosphate production and was blocked by the purinergic receptor antagonist, Reactive Blue 2, indicating that ATP was interacting with a P2y receptor. Intracellular Ca2+ release triggered by ADP was independent of both inositol phosphate production and protein tyrosine phosphorylation. Expression of the transmembrane phosphotyrosine phosphatase, CD45, had no effect on ADP-stimulated Ca2+ mobilization. Our results show that functional P2y receptors can be expressed on T-cells, and also identify a novel T-cell ADP receptor. Signals mediated by these purinergic receptors could play important roles in modulating T-cell function.
Biffen
M
M
Department of Immunology, Babraham Institute, Cambridge, U.K.
Alexander
D R
DR
D000244:Adenosine Diphosphate / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007295:Inositol Phosphates / Q000096:biosynthesis / Q000378:metabolism; D007424:Intracellular Fluid / Q000737:chemistry / Q000378:metabolism; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000378:metabolism* / Q000473:pathology*; D010766:Phosphorylation; D018048:Receptors, Purinergic P2 / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D013268:Stimulation, Chemical; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure*; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism
D007295:Inositol Phosphates; D018048:Receptors, Purinergic P2; D014443:Tyrosine; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D002118:Calcium