Action of Phospholipase $A_2$in Histamine Release from Mast Cells

비만세포에서 Histamine유리에 관여하는 Phospholipase $A_2$의 작용

  • Published : 2001.06.01


To investigate whether phospholipase $A_2$pathway is involved in histamine release of rat peritoneal mast cells, we measured histamine release in the presence of various enzyme inhibitors involved in eicosanoid pathway, such as phospholipase $A_2$, cyclooxygenase and lipoxygenase. Phospholipase $A_2$inhibitors, manoalide and OPC, significantly inhibited histamine release induced by 100 $\mu$M ATP and 1$\mu$g/ml compound 48/80. Cyclooxygenase inhibitors, ibuprofen and indomethacin, significantly inhibited ATP-induced histamine release and lipoxygenase inhibitors, baicalein and caffeic acid, also significantly inhibited. To investigate the involvement of protein kinase in ATP- and compound 48/80-induced histamine release, we observed effects of protein kinase inhibitors on histamine release. Bisindolmaleimide (protein kinase C antagonist) dose-dependently inhibited both ATP and compound 48/80-induced histamine release. Tyrosine kinase inhibitors (methyl 2,5-dihydroxy cinnamate and genistein) dose-dependently inhibited ATP and compound 48/80-induced histamine release. Protein kinase C and tyrosine kinase seem to be involved in histamine release induced by ATP and compound 48/80. These results suggest that phospholipase $A_2$pathway as well as protein kinase C and tyrosine kinase are involved in histamine release of rat peritoneal mast cells by ATP and compound 48/80.



  1. Agents Actions v.37 Influence of protein kinase C, cAMP and phosphatase activity on histamine release produced by compound 48/80 and sodium fluoride on rat mast cells Botana, L. M.;Alfonso, A.;Botana, M. A.;Vieytes, M. R.;Louzao, M. C.;Cabado, A. G.
  2. Biochem. Biophys. Res. Commun. v.117 Concerned stimulation of PI -turnover, Ca2+ -influx and histamine release in antigen-activated rat mast cells Ishizuka, Y.;Nozawa, Y.
  3. Prostaglandins Leukot. Essent. Fatty Acids v.50 no.6 Histamine release and calcium concentrations in rat mast cells are dependent on intracellular ATP: effects of prostaglandin D2. Takei, M.;Endo, K.
  4. Yakhakhoeji v.45 Effect of econazole on ATP- and compound 48/80-induced histamine release in rat peritoneal mast cells Jang, Y. U.;Lee, Y. H.;Lee, S. J.;Seo, M. H.;Yoon, J. Y.;Kim, C. J.;Sim, S. S.
  5. J. Biol. Chem. v.268 Ca2+dependent and Ca2+ -independent isozymes of protein kinase C mediate exocytosis in antigenstimulated rat basophilic RBL 2H3 cells Ozawa, K.;Szallase, Z.;Kazanietz, M. G.;Blumberg, P. M.;Mischak, H.;Mushinski, J. F.;Beaven, M. A.
  6. J. Immunol. v.155 Activation and interaction with protein kinase C of a cytoplasmic tyrosine kinase, Itk/Tsk/Emt, on FcεRI cross-linking on mast cells Kawakami, Y.;Yao, L.;Tashiro, M.;Gibson, S.;Mills, G. B.;Kawakami, T.
  7. Biochem. Biophy. Res. Commun. v.179 Tyrosine kinase-dependent phosphatidylinositol tunover and functional responses in thr FcεRI signaling pathway Deanin, G. G.;Martinez, A. M.;Pfeiffer, J. F.;Gardner, M. E.;Oliver, J. M.
  8. Nature v.353 Phosphorylation and dephosphorylation of the high-affinity receptor for immunoglobulin E immediately after receptor engagement and disengagement and disengagement Paolini, R.;Jouvin, M-H.;Kinet, J-P.
  9. J. Biol. Chem. v.267 Evidence for two distinct phosphorylation pathways activated by high affinity immunoglobulin E receptors Adamczewski, M.;Paolini, R.;Kinet, J. P.
  10. J. Immunol. v.148 Phospholipase C-gamma 1 is translocated to the membrane of rat basophilic leukemia cells in response to aggregation of IgE receptors Atkinson, T. P.;Kaliner, M. A.;Hohman, R. J.
  11. J. Biol. Chem. v.260 Simultaneous inhibitions of inositol phospholipid breakdown, arachidonic acid release, and histamine secretion in mast cells by islet-activating protein, pertussis toxin Nakamura, T.;Ui, M.
  12. J. Immunol. v.13 Phospholipase A2 stimulation during cell secretion in rat basophilic leukemia cells Garcia-Gil, M.;Siraganian, R. P.
  13. Histamine Ⅱ and anti-histamine On the general problem of the release of histamine Goth, A.;Rochae Silva M.(ed.)
  14. Agents Actions v.30 no.1-2 Histamine secretion from mast cells stimulated with ATP Jaffar, Z. h.;Pearce, F. L.
  15. Br. J. Pharmacol. v.96 Na+-K+ pump activity in rat peritoneal mast cells inhibition by extracellular calcium Kundsen, T.;Johasen, T.
  16. Anal. Biochem. v.177 A sensitive and continuous fluorometric assay for phospholipase A2 using pyrene-labeled phospholipids in the presence of serum albumin Radvanyi, F.;Jordan, L.;Russo-Marie, F.;Bon, C.
  17. Inflamm. Res. v.46 no.SUP.1 Role of phospholipase A2 in mast cell activation Varsani, M.;Pearce, F. L.
  18. Biochem. J. v.321 no.Pt 3 Differential regulation of phospholipase D and phospholipase A2 by protein kinase C in P388D1 macrophages Balsinde, J.;Balboa, M. A.;Insel, P. A.;Dennis, E. A.
  19. 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.
  20. Int. Arch. Allergy Appl. Immunol. v.66 Effects of aspirin and indomethacin on histamine release from leukocytes of patients with suspected intolerance to aspirin Conroy, M. C.;DeWeck, A. L.
  21. Br. j. Pharmacol. v.61 The inhibition of histamine release from rat peritoneal mast cells by non-steroidal anti-inflammatory drugs and its reversal by calcium Lewis, G. P.;Whittle, B. J. R.
  22. Fed. Proc. v.40 Effects of antioxidants and indomethacin on compound 48/80 induced histamine release and Ca2+ -uptake in mast cells Ranadive, N. S.;Lewis, R.