Biochemistry and Histamine

Introduction

• Histamine: Identified as an early mediator of allergies since 1932.
• Roles in:
  • Autoimmune conditions
  • Gastric acid secretion
  • Hematopoiesis
• Found in all body tissues, concentrated in lungs, basophils, and mast cells.
• Acts as a potent vasoactive agent affecting bronchial smooth muscles and itch nerves.
• Key role in inflammatory responses and various inflammatory diseases.

Fundamentals of Histamine

• Synthesis: Biogenic amine synthesized from L-histidine by L-histidine decarboxylase.
• Storage: Basophils and mast cells can produce and store histamine in granules.
• Metabolism: Metabolized by histamine-N-methyltransferase and diamine oxidase.
• Excretion: Only 2-3% excreted unchanged.

Cellular Level

• Histamine effects modulated via four receptors: H1, H2, H3, H4.
• All receptors are G-protein coupled receptors.

Function of Histamine Receptors

• H1 Receptor: Found in neurons, smooth muscles; involved in allergic reactions, sleep-wake cycles, emotions, and learning.
• H2 Receptor: Located in gastric mucosa parietal cells; mediates gastric acid secretion and vascular permeability.
• H3 Receptor: Located in histaminergic neurons; modulates neurotransmitter release.
• H4 Receptor: Found in bone marrow; involved in immune response and inflammation.

Mechanism of Action

• Immunoregulation through interaction with G protein-coupled histamine receptors.
• Affects vessels, sensory nerves, glands, and immune cell activation.

Pathophysiology

• Urticaria: Skin condition caused by histamine release, linked to allergens.
• Allergic Rhinitis: Immune overreaction to airborne allergens; symptoms managed by H1 blockers.
• Atopic Dermatitis: Chronic skin disease linked to Th1 and Th2 cytokines.
• Histamine's role in cancer and hematopoiesis noted.

Clinical Significance

• Various antihistamines (H1R, H2R) used for allergic conditions and gastric acid-related diseases.
• H3R and H4R antagonists being researched for neurodegenerative and allergic conditions.
• The ongoing research into histamine's complex interactions and potential therapeutic targets.

References

• Includes studies on the biological role and clinical implications of histamine and its receptors.