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Extracellular ATP couples to cAMP generation and granulocytic differentiation in human NB4 promyelocytic leukaemia cells
Author(s) -
Van Der Weyden Louise,
Rakyan Vardhman,
Luttrell Brian M,
Morris Michael B,
Conigrave Arthur D
Publication year - 2000
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1111/j.1440-1711.2000.t01-4-.x
Subject(s) - adenosine , extracellular , microbiology and biotechnology , adenosine triphosphate , receptor , biology , biochemistry , chemistry
Priming of NB4 promyelocytic cells with all‐ trans retinoic acid, followed by extracellular ATP in the presence of a phosphodiesterase inhibitor, elevated cAMP and activated protein kinase A. The order of potency for cAMP production was ATP (EC 50 = 95 ± 13 μmol/L) > ADP > AMP = adenosine. The order of potency of ATP analogues was 2′‐ and 3′‐ O ‐(4‐benzoylbenzoyl)‐ATP (EC 50 = 54 ± 15 μmol/L) = adenosine 5′‐ O ‐(3‐thio) triphosphate (EC 50 = 66 ± 4 μmol/L) > ATP > β,γ‐methylene ATP (EC 50 = 200 ± 55 μmol/L). Adenosine 5′‐ O ‐thiomonophosphate and adenosine 5′‐ O ‐(2‐thio) diphosphate inhibited ATP‐induced cAMP production. Differentiation also occurred as measured by increased expression of CD11b and N ‐formyl peptide receptor and changes in cell morphology. UTP did not elevate cAMP or induce differentiation, indicating that P2Y 2 , P2Y 4 , and P2Y 6 receptors were not involved. The P2Y 11 receptor, a cAMP‐linked receptor on promyelocytic HL‐60 cells, was detected in NB4 cells by reverse transcription–polymerase chain reaction and northern blotting. This receptor has the same order of potency with respect to cAMP production as that observed in HL‐60 cells.