title: Histamine release by hydrochloric acid is mediated via reactive oxygen species generation and phospholipase D in RBL-2H3 mast cells.
abstract: In order to investigate the underlying mechanism of HCl in oesophagitis, the inflammatory response to HCl was observed in RBL-2H3 mast cells. Rat basophilic leukemia (RBL-2H3) cells were used to measure histamine release, arachidonic acid (AA) release, reactive oxygen species (ROS) and peroxynitrite generation induced by HCl. Exogenous HCl increased the level of histamine release and ROS generation in a dose dependent manner, whereas it decreased the spontaneous release of [3H] AA and the spontaneous production of peroxynitrite. Mepacrine (10 microM), oleyloxyethyl phosphorylcholine (10 microM) and bromoenol lactone (10 microM) did not affect both the level of histamine release and ROS generation induced by HCl. U73122 (1 microM), a specific phospholipase C (PLC) inhibitor did not have any influence on level of histamine release and ROS generation. Propranolol (200 microM), a phospholipase D (PLD) inhibitor, and neomycin (1 mM), a nonspecific PLC and PLD inhibitor, significantly inhibited both histamine release and ROS generation. Diphenyleneiodonium (10 microM), a NADPH oxidase inhibitor, and tiron (5 mM), an intracellular ROS scavenger significantly inhibited the HCl-induced histamine release and ROS generation. These findings suggest that the inflammatory responses to HCl is related to histamine release and ROS generation, and that the ROS generation by HCl may be involved in histamine release via the PLD pathway in RBL-2H3 cells.
authors.affiliation: Department of Pathophysiology and Pharmacology, Chung-Ang University, Dongjak-gu, Seoul, Korea.
authors.forename: Chang Jong
authors.initials: CJ
authors.lastname: Kim
authors.forename: Seung Jun
authors.initials: SJ
authors.lastname: Lee
authors.forename: Moo Hyun
authors.initials: MH
authors.lastname: Seo
authors.forename: Nam Young
authors.initials: NY
authors.lastname: Cho
authors.forename: Uy Dong
authors.initials: UD
authors.lastname: Sohn
authors.forename: Moo Yeol
authors.initials: MY
authors.lastname: Lee
authors.forename: Yong Kyoo
authors.initials: YK
authors.lastname: Shin
authors.forename: Sang Soo
authors.initials: SS
authors.lastname: Sim
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects* / Q000502:physiology; D006851:Hydrochloric Acid / Q000494:pharmacology*; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D010739:Phospholipase D / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D004791:Enzyme Inhibitors; D017382:Reactive Oxygen Species; D010739:Phospholipase D; D006851:Hydrochloric Acid