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The Pharmaceutical Society of Korea (대한약학회)
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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)
  • Published : 2001.12.01
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Abstract

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.

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References

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