Springer Nature is making Coronavirus research free. View research | View latest news | Sign up for updates

Histamine release by hydrochloric acid is mediatedvia reactive oxygen species generation and phospholipase D in RBL-2H3 mast cells

  • 62 Accesses

  • 2 Citations


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 HCI 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 μM), oleyloxyethyl phosphorylcholine (10 μM) and bromoenol lactone (10 μM) did not affect both the level of histamine release and ROS generation induced by HCI. U73122 (1 μM), a specific phospholipase C (PLC) inhibitor did not have any influence on level of histamine release and ROS generation. Propranolol (200 μM), 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 μM), 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.

This is a preview of subscription content, log in to check access.


  1. Attur, M.G., Patel, R., Thakker, G., Vyas, P., Levartovsky, D., Patel, P., Naqvi, S., Raza, R., Patel, K., Abramson, D., Bruno, G., Abramson, S.B., and Amin, A.R., Differential antiinflammatory effects of immunosuppressive drugs: cyclosporin, rapamycin and FK-506 on inducible nitric oxide synthase, nitric oxide, cyclooxygenase-2 and PGE2 production.μInflamm. Res., 49, 20–6 (2000).

  2. Baas, A.S., and Berk, B.C., Differential activation of mitogenactivated protein kinases by H202 and 02- in vascular smooth muscle cells.Circ. Res., 77, 29–36 1995.

  3. Bell, N.J., and Hunt, R.H., Role of gastric acid suppression in the treatment of gastro-oesophageal reflux disease.Gut, 33, 118–24 1992.

  4. Biancani, P., Sohn, U.D., Rich, H.G., Harnett, K.M., and Behar, J., Signal transduction pathways in esophageal and lower esophageal sphincter circular muscle.Am. J. Med., 103, 23S-28S(1997).

  5. Boland, A., Delapierre, D., Mossay, D., Hans, P., and Dresse, A., Propofol protects cultured brain cells from iron ioninduced death: comparison with trolox.Eur. J. Pharmacol., 404, 21–7 (2000).

  6. Cha, S.H., Lee, W.K., Kim, K.A., Lim, Y., Han, J.S., and Lee, K.H., Effect of silica on phospholipase D activity in rat alveolar macrophages.Ind. Health, 36, 258–62 1998.

  7. Chakraborti, S., Batabyal, S.K., and Chakraborti, T., Role of hydroxyl radical in the stimulation of arachidonic acid release caused by H202 in pulmonary smooth muscle cells: protective effect of anion channel blocker.Mol. Cell Biochem., 146, 91–8 1995.

  8. Dana, R., Leto, T.L., Malech, H.L., and Levy, R., Essential requirement of cytosolic phospholipase A2 for activation of the phagocyte NADPH oxidase.J. Biol. Chem., 273, 441–5 1998.

  9. Huang, Z., Payette, P., Abdullah, K., Cromlish, W.A., and Kennedy, B.P, Functional identification of the active-site nucleophile of the human 85-kDa cytosolic phospholipase A2.Biochemistry, 35, 3712–21 (1996).

  10. Jesus, B., Suzanne, E.B., Ismael, D.B., and Edward, A.D., Arachidonic acid mobilization in P388D1 macrophages is controlled by two distinct Ca2+-dependent phospholipase A2 enzymes.Proc. Natl. Acad. Sci. USA., 91, 11060–4 1994.

  11. Matsui, T., Suzuki, Y., Yamashita, K., Yoshimaru, T., Suzuki-Karasaki, M., Hayakawa, S., Yamaki, M., and Shimizu, K., Diphenyleneiodonium prevents reactive oxygen species generation, tyrosine phosphorylation, and histamine release in RBL-2H3 mast cells.Biochem. Biophys. Res. Commun., 276, 742–8 2000.

  12. Palomba, L., Sestili, P., Guidarelli, A., Sciorati, C., Clementi, E., Fiorani, M., and Cantoni, O., Products of the phospholipase A2 pathway mediate the dihydrorhodamine fluorescence response evoked by endogenous and exogenous peroxynitrite in PC12 cells.Free Radic. Biol. Med., 29, 783–9 2000.

  13. Petrone, W.F., English, D.K., Wong, K., and McCord, J.M., Free radicals and inflammation: superoxide-dependent activation of a neutrophil chemotactic factor in plasma.Proc. Natl. Acad. Sci. USA., 77, 1159–63 1980.

  14. Raguenes-Nicol, C., Russo-Marie, F., Domage, G., Diab, N., Solito, E., Dray, F., and Mace, J.L., Streichenberger G. Antiinflammatory mechanism of alminoprofen: action on the phospholipid metabolism pathway.Biochem. Pharmacol., 57, 433–43 (1999).

  15. Rao, G.N., Runge, M.S., and Alexander, R.W., Hydrogen peroxide activation of cytosolic phospholipase A2 in vascular smooth muscle cells.Biochim. Biophys. Acta, 1265, 67–72 1995.

  16. Shore, P.A., Burkhalter, A., and Cohn, V.H., A method for the fluorometric assay of histamine in tissues.J. Pharmacol. Exp. Ther., 127, 182–6 1959.

  17. Sohn, U.D., Harnett, K.M., Cao, W., Rich, H., Kim, N., Behar, J., and Biancani, P., Acute experimental esophagitis activates a second signal transduction pathway in cat smooth muscle from the lower esophageal sphincter.J. Pharmacol. Exp. Ther., 283, 1293–304 1997.

  18. Varsani, M., and Pearce, F.L., Role of phospholipase A2 in mast cell activation.Inflamm. Res., 46, S9–10 1997.

Download references

Author information

Correspondence to Uy Dong Sohn or Moo Yeol Lee or Yong Kyoo Shin or Sang Soo Sim.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Kim, C.J., Lee, S.J., Seo, M.H. et al. Histamine release by hydrochloric acid is mediatedvia reactive oxygen species generation and phospholipase D in RBL-2H3 mast cells. Arch Pharm Res 25, 675–680 (2002).

Download citation

Key words

  • Histamine
  • Reactive oxygen species
  • Peroxynitrite
  • Phospholipase