Histamine Physiology

Histamine is a biogenic amine involved in:

• Immediate hypersensitivity reactions
• Gastric acid secretion
• Neurotransmission
• Inflammatory signaling

This page covers synthesis, storage, release, and physiologic effects.

Histamine is synthesized from the amino acid histidine.

Reaction:

Histidine → (Histidine decarboxylase) → Histamine

• Enzyme: Histidine decarboxylase
• Requires pyridoxal phosphate (Vitamin B6)

Primary sites of synthesis:

• Mast cells
• Basophils
• Enterochromaffin-like (ECL) cells of the stomach
• Certain neurons in the CNS

• Stored in cytoplasmic granules
• Complexed with heparin and proteoglycans
• Preformed mediator (ready for immediate release)

• Circulating granulocytes
• Contain histamine granules similar to mast cells

• Release histamine to stimulate acid secretion

Histamine is NOT synthesized on demand in mast cells — it is preformed and stored.

• Allergen cross-links IgE bound to FcεRI receptors
• Calcium influx
• Rapid degranulation
• Immediate mediator release

This produces:

• Urticaria
• Bronchoconstriction
• Hypotension
• Anaphylaxis

See: Type I Hypersensitivity

Certain agents directly trigger mast cell degranulation:

• Opioids
• Radiocontrast
• Vancomycin (Red Man Syndrome)
• Physical stimuli (cold, pressure)

This is sometimes called “pseudoallergic” activation.

In the stomach:

• Vagus nerve → Acetylcholine
• Gastrin

→ Stimulate ECL cells

→ Histamine release
→ H2 receptor activation on parietal cells
→ ↑ Gastric acid secretion

See: H2 Blockers

There are four known histamine receptors:

See detailed signaling: Histamine Receptor Signaling

• Endothelial contraction → Capillary leakage → Edema
• Nitric oxide release → Vasodilation
• Sensory nerve stimulation → Pruritus
• Bronchial smooth muscle contraction → Wheezing
• Increased mucus secretion

Clinical correlates:

• Allergic rhinitis
• Urticaria
• Asthma
• Anaphylaxis

• Histamine
• Tryptase
• Leukotrienes
• Prostaglandins

• Eosinophils
• Cytokines (IL-4, IL-5, IL-13)
• Sustained inflammation

Histamine dominates early symptoms (itching, redness, sneezing).

Histamine is rapidly metabolized by:

• Histamine-N-methyltransferase (HNMT)
• Diamine oxidase (DAO)

Short half-life in circulation.

Blocking histamine signaling forms the basis of:

• H1 Antihistamines
• H2 Blockers
• Anaphylaxis management (Epinephrine)

Histamine explains:

• Why allergic reactions are rapid
• Why itching occurs
• Why congestion develops
• Why anaphylaxis causes vasodilation and shock

• Histamine is preformed in mast cell granules.
• H1 receptors signal through Gq → IP3 → Ca²⁺.
• H2 receptors signal through Gs → cAMP.
• Histamine causes both vasodilation AND increased vascular permeability.
• Decongestants treat symptoms, not histamine release.