title: P2Z purinoceptor, a special receptor for apoptosis induced by ATP in human leukemic lymphocytes.
abstract: OBJECTIVE
  To investigate the role of purinergic P2Z receptors for apoptosis of human leukemic lymphocytes mediated by extracellular adenosine triphosphate (ATP).
  
  
  METHODS
  A total of 13 B-chronic lymphocytic leukemia (CLL) patients were studied. Exposure of leukemic lymphocytes with (n = 8) or without (n = 5) P2Z receptors to ATP, benzoylbenzoic-ATP (BzATP), 2-methylthio-ATP (2MeSATP), adenosine-5' [gamma-thio] triphosphate (ATP-gamma S), and other nucleosides for 8 h in vitro. Apoptosis was detected by electron microscopy (EM), agarose gel electrophoresis, and the quantitative assay-TdT assay.
  
  
  RESULTS
  Apoptosis was detected only in leukemic lymphocytes with P2Z receptors. Using a quantitative assay, ATP-induced DNA strand breaks were found to occur specifically with BzATP, ATP and 2MeSATP, but not for analogue ATP-gamma S nor other nucleosides. Meanwhile, ATP-induced DNA fragmentation was fully blocked by pretreatment with oxidized ATP (OxATP), a compound recently shown to block P2Z receptors. Also, it is shown that the Ca2+/calmodulin complex plays a role in the regulation of the apoptosis induced by ATP on CLL cells, because an antagonist of this complex, 1-[N, O-bis (5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperazine (KN-62) was found to inhibit the ATP-induced apoptosis. Furthermore, choline, an inhibitor of phospholipase D (PLD), is first shown to partially inhibit ATP-induced apoptosis.
  
  
  CONCLUSIONS
  These data indicate that P2Z receptors on lymphocytes play an important role in the apoptosis induced by ATP in vitro.
authors.affiliation: Department of Laboratory Medicine, First Hospital, West China University of Medical Sciences, Chengdu 610041, China.
authors.forename: L
authors.initials: L
authors.lastname: Peng
authors.forename: C J
authors.initials: CJ
authors.lastname: Bradley
authors.forename: J S
authors.initials: JS
authors.lastname: Wiley
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002469:Cell Separation; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000378:metabolism / Q000473:pathology*; D008214:Lymphocytes / Q000473:pathology*; D018048:Receptors, Purinergic P2 / Q000502:physiology*; D058486:Receptors, Purinergic P2X7
chemical_list: C546468:P2RX7 protein, human; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; D000255:Adenosine Triphosphate