title: Interactions between nitric oxide and arachidonic acid in lung epithelial cells: possible roles for peroxynitrite and superoxide.
abstract: This study investigated interactions between nitric oxide synthesis and phospholipase A2 (PLA2) activation in lung epithelial cells. Nitrite formation, inducible nitric oxide synthase expression, and [3H]arachidonic acid (AA) release were determined following treatment with: (1) the nitric oxide synthase inhibitors N(G)-nitro-L-arginine methyl esther (L-NAME) and aminoguanidine; (2) arachidonyl trifluoromethyl ketone (AACOCF3), a specific cytosolic PLA2 inhibitor; (3) S-morpholinosydnonimine (SIN-1), a nitric oxide donor which provokes peroxynitrite formation; (4) trolox, a free radical scavenger, and (5) the AA release agonists calcium ionophore, phorbol 12-myristate 13-acetate, and sodium vanadate. The results demonstrated that (1) L-NAME and aminoguanidine inhibited agonist-induced AA release by 40 and 65%, respectively; (2) AACOCF3 inhibited nitrite formation and inducible nitric oxide synthase expression in a dose-dependent manner; (3) SIN-1, together with AA release agonists, significantly increased the AA output, and (4) trolox counteracted the SIN-1 effects. Our results demonstrate cross talk between nitric oxide synthase and PLA(2) pathways, with a possible intermediary role for peroxynitrite and superoxide.
authors.affiliation: Institute of Biochemistry, Faculty of Agricultural, Food and Environmental Quality Sciences, The Hebrew University of Jerusalem, Rehovot, Israel.
authors.forename: Sarit
authors.initials: S
authors.lastname: Offer
authors.forename: Abraham
authors.initials: A
authors.lastname: Eliraz
authors.forename: Gershon
authors.initials: G
authors.lastname: Fink
authors.forename: Aliza H
authors.initials: AH
authors.lastname: Stark
authors.forename: Zecharia
authors.initials: Z
authors.lastname: Madar
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D002461:Cell Line, Transformed; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000502:physiology; D052247:Nitric Oxide Synthase Type II; D030421:Peroxynitrous Acid / Q000502:physiology*; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000502:physiology; D054467:Phospholipases A2; D051381:Rats; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013481:Superoxides / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D013481:Superoxides; D030421:Peroxynitrous Acid; D016718:Arachidonic Acid; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D010741:Phospholipases A; D054467:Phospholipases A2