Monochloramine Potently Inhibits Arachidonic Acid Metabolism in Rat Platelets

Biochem Biophys Res Commun. 2006 May 26;344(1):140-5. doi: 10.1016/j.bbrc.2006.03.120. Epub 2006 Mar 29.

Abstract

In the present study, the effects of hypochlorous acid (HOCl), monochloramine (NH(2)Cl), glutamine-chloramine (Glu-Cl) and taurine-chloramine (Tau-Cl) on the formation of 12-lipoxygenase (LOX) metabolite, 12-HETE, and cyclooxygenase (COX) metabolites, TXB(2), and 12-HHT, from exogenous arachidonic acid (AA) in rat platelets were examined. Rat platelets (4x10(8)/ml) were preincubated with drugs for 5min at 37 degrees C prior to the incubation with AA (40microM) for 2min at 37 degrees C. HOCl (50-250microM) showed an inhibition on the formation of LOX metabolite (12-HETE, 5-67% inhibition) and COX metabolites (TXB(2), 33-73% inhibition; 12-HHT, 27-74% inhibition). Although Tau-Cl and Glu-Cl up to 100microM were without effect on the formation of 12-HETE, TXB(2) and 12-HTT, NH(2)Cl showed a strong inhibition on the formation of all three metabolites (10-100microM NH(2)Cl, 12-HETE, 21-92% inhibition; TXB(2), 58-94% inhibition; 12-HHT, 36-92% inhibition). Methionine reversed a reduction of formation of LOX and COX metabolites induced by NH(2)Cl, and taurine restoring that induced by both NH(2)Cl and HOCl. These results suggest that NH(2)Cl is a more potent inhibitor of COX and LOX pathways in platelets than HOCl, and taurine and methionine can be modulators of NH(2)Cl-induced alterations in the COX and LOX pathways in vivo.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid / metabolism
  • Animals
  • Arachidonic Acid / metabolism*
  • Blood Platelets / drug effects*
  • Blood Platelets / enzymology
  • Blood Platelets / metabolism
  • Chloramines / chemistry
  • Chloramines / pharmacology*
  • Cyclooxygenase Inhibitors / chemistry
  • Cyclooxygenase Inhibitors / pharmacology*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Fatty Acids, Unsaturated / metabolism
  • Glutamine / analogs & derivatives
  • Glutamine / pharmacology
  • Hypochlorous Acid / pharmacology
  • Lipoxygenase Inhibitors*
  • Prostaglandin-Endoperoxide Synthases / drug effects*
  • Rats
  • Taurine / analogs & derivatives
  • Taurine / pharmacology
  • Thromboxane B2 / metabolism

Substances

  • Chloramines
  • Cyclooxygenase Inhibitors
  • Enzyme Inhibitors
  • Fatty Acids, Unsaturated
  • Lipoxygenase Inhibitors
  • glutamine chloramine
  • Glutamine
  • Taurine
  • Arachidonic Acid
  • 12-hydroxy-5,8,10-heptadecatrienoic acid
  • N-chlorotaurine
  • Thromboxane B2
  • 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid
  • Hypochlorous Acid
  • Prostaglandin-Endoperoxide Synthases
  • chloramine