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[Physiological function mediated by histamine synthesis].

Satoshi Tanaka1

  • 1Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan. satoshit@pharm.kyoto-u.ac.jp

Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan
|July 24, 2003
PubMed
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Histamine synthesis, regulated by histidine decarboxylase (HDC), impacts allergies and gastric acid. HDC-deficient mice reveal histamine

Area of Science:

  • Immunology
  • Molecular Biology
  • Physiology

Background:

  • Histamine mediates crucial physiological functions including inflammation, allergy, and neurotransmission.
  • Regulation of histamine synthesis and its broader physiological roles require further elucidation.
  • Previous research primarily focused on histamine receptors and release mechanisms.

Purpose of the Study:

  • To investigate the regulation of histamine synthesis by histidine decarboxylase (HDC) in mast cells.
  • To explore the physiological roles of histamine using HDC-deficient mice.
  • To understand histamine's involvement in allergic responses, gastric acid secretion, mast cell development, and anti-tumor immunity.

Main Methods:

  • Utilized immunocytochemical approaches with anti-HDC antibodies to study histamine synthesis compartments.

Related Experiment Videos

  • Investigated IgE-mediated induction of histamine synthesis in mast cells.
  • Generated and analyzed HDC-deficient mice via gene targeting to assess histamine's physiological functions.

    • Main Results:

    • Histamine synthesis occurs in mast cell cytosol and granules, regulated by HDC posttranslational modification.
    • IgE significantly induces histamine synthesis in mast cells, independent of antigens.
    • HDC-deficient mice confirmed histamine's essential role in type I allergy and gastric acid secretion; also revealed histamine's regulation of mast cell proliferation/differentiation and suppression of anti-tumoral cytokines (interferon-gamma, tumor necrosis factor-alpha) via H2 receptors.

    Conclusions:

    • Histamine synthesis regulation by HDC is complex, occurring in distinct cellular compartments.
    • Histamine plays multifaceted roles beyond allergy, influencing mast cell dynamics and tumor microenvironment.
    • HDC-deficient mice provide a valuable model for dissecting histamine's physiological and pathological contributions.