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Histamine and arachidonic acid (AA) release was measured using the P2-purinoceptor antagonists, phospholipase A2 (PLA2) and cyclooxygenase (COX)/lipoxygena se (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 manners whereas adenosine did not. PPADS (a selective P2X-purlnoceptor 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 PLA2 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]AA release by 81% and 39%, respectively. ATP-induced histamine release was significantly inhibited by a variety of protein kinase inhibitors, such as bisindol-maleimide, 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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