ATP-induced histamine release is in part related to phospholipase A2-mediated arachidonic acid metabolism in rat peritoneal mast cells.
Histamine and arachidonic acid (AA) release was measured using the P2-purinoceptor antagonists, phospholipase A2 (PLA2) 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 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 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.
Lee
Y H
YH
Department of Pathophysiology, College of Pharmacy, Chung-Ang University, Dongak-gu, Seoul, Korea.
Lee
S J
SJ
Seo
M H
MH
Kim
C J
CJ
Sim
S S
SS
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D006636:Histamine Release / Q000187:drug effects*; D008084:Lipoxygenase / Q000502:physiology; D008297:Male; D008407:Mast Cells / Q000378:metabolism*; D010529:Peritoneal Cavity / Q000166:cytology; D010741:Phospholipases A / Q000502:physiology*; D054467:Phospholipases A2; D011493:Protein Kinase C / Q000502:physiology; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018048:Receptors, Purinergic P2 / Q000502:physiology
D018048:Receptors, Purinergic P2; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D016718:Arachidonic Acid; D011732:Pyridoxal Phosphate; D000255:Adenosine Triphosphate; D008084:Lipoxygenase; D011493:Protein Kinase C; D010741:Phospholipases A; D054467:Phospholipases A2