title: Extracellular ATP activates mast cells via a mechanism that is different from the activation induced by the cross-linking of Fc receptors.
abstract: In this study, the extracellular ATP (ATPo)-induced biochemical events were elucidated by comparing them with either the Fc epsilon RI- or Fc gamma R-induced events in the mouse mast cell line MC9. The omission of extracellular Ca2+ almost completely abolished the elevation of intracellular Ca2+ ([Ca2+]i) in the ATPo-stimulated cells, but only suppressed the second phase of the increase of [Ca2+]i in FcR-stimulated cells, thus suggesting that the ATPo-induced elevation of [Ca2+]i is totally dependent on the entry of extracellular Ca2+. Pretreatment with genistein, which inhibits protein kinases, especially protein tyrosine kinase, inhibited the FcR-triggered increase of [Ca2+]i, but not the ATPo-triggered one; however, such pretreatment did suppress both ATPo- and FcR-mediated beta-hexosaminidase release. An immunoblot analysis revealed that both ATPo and the cross-linking of FcRs led to tyrosine phosphorylation of 44- and 110-kDa proteins, which thus suggested that these tyrosine-phosphorylated proteins are involved in a modulation of the degranulation process following an elevation of [Ca2+]i. Pretreatment with PMA inhibited the FcR-induced [Ca2+]i increase, while not inhibiting the ATPo-induced one, thus suggesting that ATPo can mobilize [Ca2+]i even when protein kinase C (PKC) has already been activated. Pretreatment of calphostin C, a specific PKC inhibitor, had little effect on the ATPo-mediated beta-hexosaminidase secretion, thus indicating that the ATPo-induced degranulation is not mediated by PKC. Taken together, these results demonstrate that ATPo activates MC9 mast cells by a mechanism that is different from the activation induced by the cross-linking of FcRs.
authors.affiliation: Department of Psychosomatic Medicine, Kyushu University School of Medicine, Fukuoka, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Sudo
authors.forename: K
authors.initials: K
authors.lastname: Tanaka
authors.forename: Y
authors.initials: Y
authors.lastname: Koga
authors.forename: Y
authors.initials: Y
authors.lastname: Okumura
authors.forename: C
authors.initials: C
authors.lastname: Kubo
authors.forename: K
authors.initials: K
authors.lastname: Nomoto
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D003432:Cross-Linking Reagents; D005110:Extracellular Space / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D019833:Genistein; D006636:Histamine Release / Q000187:drug effects*; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D007529:Isoflavones / Q000494:pharmacology; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D009281:Naphthalenes / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011961:Receptors, Fc / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D010738:Type C Phospholipases / Q000187:drug effects / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D001619:beta-N-Acetylhexosaminidases / Q000187:drug effects / Q000378:metabolism
chemical_list: D003432:Cross-Linking Reagents; D007529:Isoflavones; D009281:Naphthalenes; D011961:Receptors, Fc; D014443:Tyrosine; D015544:Inositol 1,4,5-Trisphosphate; D000255:Adenosine Triphosphate; D019833:Genistein; D011493:Protein Kinase C; D010738:Type C Phospholipases; D001619:beta-N-Acetylhexosaminidases; C058819:calphostin C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium