Histamine

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Histamine

Introduction

  • Autacoids: histamine, serotonin, endogenous peptides, prostaglandins, leukotrienes
  • Definition -- autacoids: "self-remedy" -- local hormones

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  • Chemistry/Pharmacokinetics
    • Formation -- decarboxylation of L-histidine
    • Inactivation:
      1. formation of methylhistamine
      2. oxidation step
      3. Usually little histamine excreted unchanged, except in the presence of neoplastic disease.
        •  systemic mastocytosis
        •  gastric carcinoid
        •  urticaria pigmentosa
    • Tissue Distribution:
      • Primary site -- granules in mast cells or basophils
        • Mast cells:
          • especially prominent that cites a potential tissue injury
        • Other sites:
          • Center nervous system -- neurotransmitter
          • Fundus of the stomach -- enterochromaffin-like cells:
            •  major acid secretagogues -- activates acid-producing mucosal parietal cells

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  • Histamine: Storage and Release
    • Immunologic Release:
      • Most important mechanism
      • Mast cells, if sensitized by surface IgE antibodies, degranulate when exposed specific antigen
        •  Degranulation:
          • immediate (type I) allergic reaction
          • calcium-dependent, energy dependent
          • Release components:
            1. histamine
            2. ATP
            3. other mediators present in granules
          •  Degranulation may also occurred subsequent to IgG-or IgM-mediated immune reactions
        • Release regulation:
          • present in most mast cells (not lung)

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      • Histamine Modulation: immunologic/inflammatory responses
        • Histamine -- following local injury:
          1. local vasodilation
          2. acute inflammation mediator release--
            • inflammatory cells
              1. neutrophils
              2. eosinophils
              3. basophils
              4. monocytes
              5. lymphocytes
        • Histamine --
          • inhibits some T and B lymphocyte function
          • inhibits release of lysosomal contents
          • Mechanism of Action:
            1. H2 receptor activation
            2. increasing intracellular cAMP

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    •  Mechanical/Chemical Release:
      • Histamine displacement:
        • Morphine, tubocurarine: displacement of histamine from heparin-protein complex
        • Degranulation:
          • chemical or mechanical injury to mast cells
          • chemicals
Burkhalter, A, Julius, D.J. and Katzung, B. Histamine, Serotonin and the Ergot Alkaloids (Section IV. Drugs with Important Actions on Smooth Muscle), in Basic and Clinical Pharmacology, (Katzung, B. G., ed) Appleton-Lange, 1998, pp 261-286.