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Histamine-induced inhibition of leukotriene biosynthesis in human neutrophils: involvement of the H2 receptor and cAMP.

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  • Author(s): Flamand N;Flamand N; Plante H; Picard S; Laviolette M; Borgeat P
  • Source:
    British journal of pharmacology [Br J Pharmacol] 2004 Feb; Vol. 141 (4), pp. 552-61. Date of Electronic Publication: 2004 Jan 26.
  • Publication Type:
    Journal Article; Research Support, Non-U.S. Gov't
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Wiley Country of Publication: England NLM ID: 7502536 Publication Model: Print-Electronic Cited Medium: Print ISSN: 0007-1188 (Print) Linking ISSN: 00071188 NLM ISO Abbreviation: Br J Pharmacol Subsets: MEDLINE
    • Publication Information:
      Publication: London : Wiley
      Original Publication: London, Macmillian Journals Ltd.
    • Subject Terms:
      Sulfonamides*; Cyclic AMP/*physiology ; Histamine/*pharmacology ; Leukotrienes/*biosynthesis ; Neutrophils/*metabolism ; Receptors, Histamine H2/*metabolism; Arachidonate 5-Lipoxygenase/metabolism ; Arachidonic Acid/metabolism ; Calcium/metabolism ; Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors ; Cyclic AMP-Dependent Protein Kinases/metabolism ; Depression, Chemical ; Dose-Response Relationship, Drug ; Enzyme Inhibitors/pharmacology ; Histamine Agonists/pharmacology ; Histamine Antagonists/pharmacology ; Humans ; In Vitro Techniques ; Isoquinolines/pharmacology ; Leukotriene B4/biosynthesis ; Neutrophils/drug effects ; Nuclear Envelope/drug effects ; Nuclear Envelope/enzymology ; Phospholipases A/metabolism ; Stimulation, Chemical ; Translocation, Genetic/genetics
    • Abstract:
      1. Histamine is generally regarded as a pro-inflammatory mediator in diseases such as allergy and asthma. A growing number of studies, however, suggest that this autacoid is also involved in the downregulation of human polymorphonuclear leukocyte (PMN) functions and inflammatory responses through activation of the Gs-coupled histamine H(2) receptor. 2. We report here that histamine inhibits thapsigargin- and ligand (PAF and fMLP)-induced leukotriene (LT) biosynthesis in human PMN in a dose-dependent manner. 3. The suppressive effect of histamine on LT biosynthesis was abrogated by the histamine H(2) receptor antagonists cimetidine, ranitidine, and tiotidine. In contrast, the histamine H(1), H(3), and H(4) receptor antagonists used in this study were ineffective in counteracting the inhibitory effect of histamine on the biosynthesis of LT in activated human PMN. 4. The inhibition of LT biosynthesis by histamine was characterized by decreased arachidonic acid release and 5-lipoxygenase translocation to the nuclear membrane. 5. Incubation of PMN with the cAMP-dependent protein kinase (PKA) inhibitor N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinoline-sulfonamide prevented the inhibitory effect of histamine on LT biosynthesis, suggesting an important role for PKA in this effect of histamine on LT biosynthesis in PMN. 6. These data provide the first evidences that, similarly to adenosine and prostaglandin E(2), histamine is a potent suppressor of LT biosynthesis, and support the concept that histamine may play a dual role in the regulation of inflammation.
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    • Grant Information:
      46187-1 Canada CAPMC CIHR
    • Accession Number:
      0 (Enzyme Inhibitors)
      0 (Histamine Agonists)
      0 (Histamine Antagonists)
      0 (Isoquinolines)
      0 (Leukotrienes)
      0 (Receptors, Histamine H2)
      0 (Sulfonamides)
      1HGW4DR56D (Leukotriene B4)
      27YG812J1I (Arachidonic Acid)
      820484N8I3 (Histamine)
      E0399OZS9N (Cyclic AMP)
      EC 1.13.11.34 (Arachidonate 5-Lipoxygenase)
      EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
      EC 3.1.1.32 (Phospholipases A)
      M876330O56 (N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide)
      SY7Q814VUP (Calcium)
    • Publication Date:
      Date Created: 20040128 Date Completed: 20041014 Latest Revision: 20250529
    • Publication Date:
      20250529
    • Accession Number:
      PMC1574237
    • Accession Number:
      10.1038/sj.bjp.0705654
    • Accession Number:
      14744809