Histamine Release by Hydrochloric Acid is Mediated via Reactive Oxygen Species Generation and Phospholipase D in RBL-2H3 Mast Cells

  • Kim, Chang-Jong (Department of Pathophysiology and Pharmacology, Chung-Ang University) ;
  • Lee, Seung-Jun (Department of Pathophysiology and Pharmacology, Chung-Ang University) ;
  • Seo, Moo-Hyun (Department of Pathophysiology and Pharmacology, Chung-Ang University) ;
  • Cho, Nam-Young (Department of Pathophysiology and Pharmacology, Chung-Ang University) ;
  • Sohn, Uy-Dong (Department of Pathophysiology and Pharmacology, Chung-Ang University) ;
  • Lee, Moo-Yeol (College of Pharmacy, Department of Physiology and Pharmacology, Chung-Ang University) ;
  • Shin, Yong-Kyoo (College of Medicine, Chung-Ang University) ;
  • Sim, Sang-Soo (Department of Pathophysiology, College of Pharmacy, Chung-Ang University)
  • Published : 2002.10.01

Abstract

In order to investigate the underlying mechanism of HCI in oesophagitis, the inflammatory response to HCI 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 HCI. Exogenous HCl increased the level of histamine release and ROS generation in a dose dependent manner, whereas it decreased the spontaneous release of [$^3$H] M and the spontaneous production of peroxynitrite. Mepacrine (10 $\mu$M), oleyloxyethyl phosphorylcholine (10 $\mu$M) and bromoenol lactone (10 $\mu$M) did not affect both the level of histamine release and ROS generation induced by HCI. U73122 (1 $\mu$M), a specific phospholipase C (PLC) inhibitor did not have any influence on level of histamine release and ROS generation. Propranolol (200 $\mu$M), 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 $\mu$M), a NADPH oxidase inhibitor, and tiron (5 mM), an intracellular ROS scavenger significantly inhibited the HCI-induced histamine release and ROS generation. These findings suggest that the inflammatory responses to HCI is related to histamine release and ROS generation, and that the ROS generation by HCI may be involved in histamine release via the PLD pathway in RBL-2H3 cells.

Keywords

References

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