ATP-Induced Histamine Release Is in Part Related to Phospholipase $A_2$-Mediated Arachidonic Acid Metabolism in Rat Peritoneal Mast Cells

  • Lee, Yun-Hye (Department of Pathophysiology, College of Pharmacy, Chung-Ang University) ;
  • Lee, Seung-Jun (Department of Pathophysiology, College of Pharmacy, Chung-Ang University) ;
  • Seo, Moo-Hyun (Department of Pathophysiology, College of Pharmacy, Chung-Ang University) ;
  • Kim, Chang-Jong (Department of Pathophysiology, College of Pharmacy, Chung-Ang University) ;
  • Sim, Sang-Soo (Department of Pathophysiology, College of Pharmacy, Chung-Ang University)
  • 발행 : 2001.12.01


Histamine and arachidonic acid (AA) release was measured using the P2-purinoceptor antaongists, phospholipase $A_2{\;}(PLA_2)$ and cyclooxygenase (COX)/lipoxygenase (LOX) inhibitors to determine whether or not ATP-induced histamine release is associated with arachidonic acid (AA) release in rat peritoneal mast cells. ATP increased histamine release in a dose dependent manner, whereas adenosine did not. PPADS (a selective P2X-purinoceptor antagonist) and suramin (a nonselective P2X,2Y-purinoceptor antagonist) inhibited ATP-induced histamine release in a dose dependent manner. However, RB-2 (a P2Y-purinoceptor antagonist) did not block ATP-induced histamine release. Manoalide and oleyloxyethyl phosphorylcholine (OPC), secretory PLA$_2$ inhibitors, also inhibited ATP-induced histamine release dose-dependently. Both COX inhibitors (ibuprofen and indomethacin) and LOX inhibitors (baicalein and caffeic acid) inhibited ATP-induced histamine in a dose dependent manner. ATP significantly increased [$^3H$]AA release by 54%. PPADS and suramin significantly inhibited ATP-induced [3H]Ph release by 81% and 39%, respectively. ATP-induced histamine release was significantly inhibited by a variety of protein kinase inhibitors, such as bisindolmaleimide, genistein, methyl 2,5-dihydroxycinnamate, W-7 and trifluoperazine. Overall, the results suggest that ATP-induced histamine release is in part related to the PLA2-mediated AA metabolism and P2X-purinoceptors.


  1. J. Biol. Chem. v.271 Distinct roles in signal transduction for each of the phospholipase A₂enzymes present in P388D1 macrophages Balsinde,J.;Dennis,E.A.
  2. Proc. Natl. Acad. Sci. v.95 Functional coupling between secretory phospholipase A₂and cyclooxygenase-2 and its regulation by cytosolic group IV phospholipase A₂ Balsinde,J.;Balboa,M.A.;Dennis,E.A.
  3. Biochem. J. v.321 Differential regulation of phospholipase D and phospholipase A₂by protein kinase C in P388D1 macrophages Balsinde,J.;Balboa,M.A.;Inse,P.A.;Dennis,E.A.
  4. Br. J. Pharmacol v.59 The effects of non-steroidal anti-inflammatory drugs on adenosine triphosphate content and histamine release from rat peritoneal cell suspensions rich in mast cells Champion,G.D.;Day,R.O.;Wade,D.N.
  5. Int. Arch. Allergy Appl. Immunol. v.66 Effects of aspirin and indomethacin on histamine realease form leukocytes of patients with suspected intolerance to aspirin Conroy,M.C.;DeWeck,A.L.
  6. Acta Physiol. Scand. v.71 Histamine release from isolated rat peritoneal mast cells induced by adenosine 5¹-triphosphate Diamant,B.;Kruger,P.G.
  7. Acta Pharmacol. Toxicol. v.34 Interaction of ATP and calcium on the rat mast cell : Effect on histamine release Dahlquist,R.;Diamant,B.
  8. Agents Actions v.24 Comparative studies on the effect of non-steroidal anti-inflammatory drugs (NSAID) on histamine release from mast cells of the rat and guinea pig Gomes,J.C.;Pearce,F.L.
  9. Agents Actions v.22 The role of a Ca²+/calmodulin dependent plasma membrane Ca²+ channel during concanavalin A activation of MC9 mast cells Gulbenkian,A.;Myers,J.;Egan,R.W.;Siegel,M.I.
  10. Immunopharmacology v.18 Histamine release from betaescin-permeabilized rat peritoneal mast cells and its inhibition by intracellular Ca²+ blockers, calmodulin inhibitors and cAMP Izushi,K.;Tasaka,K.
  11. Agents Actions v.30 Histamine secretion from mast cells stimulated with ATP. Jaffar,Z.H.;Pearce,F.L.
  12. Agents Actions v.40 Some characteristics of the ATP-induced histmine release from and permeabilization of rat mast cells Jaffar,Z.H.;Pearce,F.L.
  13. Proc. Natl. Acad. Sci. v.91 Arachidonic acid mobilization in P3881D1 macrophages in controlled by two distinct Ca²+ -dependant phospholipase A₂enzymes Jesus,B.;Suzanne,E.B.;Ismael,D.B.;Edward,A.D.
  14. Br. J. Pharmacol. v.96 $Na^+$-K^+$ pump activity in rat peritoneal mast cells inhibition by extracellular calcium Knudsen,T.;Johansen,T.
  15. Br. J. Pharmacol. v.61 The inhibition of histamine release from rat peritoneal mast cells by nonsteroidal anti-inflammatory drugs and its reversal by calcium Lewis,G.P.;Whittle,B.J.R.
  16. MC9. Prostaglandins v.29 Ionophore-simulated lipoxygenase activity and histamine release in a cloned murine mast cell Musch,M.W.;Bryant,R.W.;Coscollueala,C.;Myers,R.F.;Siegel,M.I.
  17. J. Biol. Chem. v.268 $Ca^{2+}$-dependent and $Ca^{2+}$-independent isozymes of protein kinase C mediate exocytosis in antigen-stimulated rat basophilic RBL.2H3 cells Ozawa,K.;Szallasi,Z;Kazanietz,M.G.;Blumberg,P.M.;Mischak,H.;Mushinski,J.F.;Beaven,M.A.
  18. J. Pharmacol. Exp. Ther. v.127 A method for the fluorometric assay of histamine in tissues Shore,P.A.;Burkhalter,A.;Cohn,V.H.
  19. Gen. Pharmacol. v.14 Effects of calmodulin inhibitor on histamine release from rat peritoneal mast cells induced by concanavalin A and inophore A23187 Suzuki,T.;Ohishi,K.;Uchida,M.
  20. Biochem. J. v.234 Antigen-stimulated metabolism of inositol phospholipids in the cloned murine mast-cell line MC9 Musch,M.W.;Siegel,M.I.
  21. Inflamm. Res. v.46 Role of phospholipase A₂in mast cell activation Varsani,M.;Pearce,F.L.