Histamines

Histamine is an organic amine derived from the amino acid histidine by the enzyme histidine decarboxylase. In humans, it is stored in the granules of mast cells and basophils and is also produced by enterochromaffin-like cells in the stomach and certain neurons. It serves as both a local mediator of inflammatory and allergic responses and as a neurotransmitter in the brain.

Histamine exerts its effects through four G protein–coupled receptors, H1–H4. H1 receptors mediate vasodilation, increased vascular permeability, bronchoconstriction, and itch; H2 receptors promote gastric acid secretion and modulate immune cell activity; H3 receptors regulate histamine release and other neurotransmitter signaling; H4 receptors are involved in immune cell trafficking and function.

Release is triggered by allergens, pathogens, tissue injury, and other immune stimuli. Upon release, histamine increases vascular permeability, contributes to edema, causes smooth muscle contraction in the airways, and mediates itch and pain. In the brain, histamine acts as a wake-promoting neurotransmitter and influences appetite and arousal.

Histamine is rapidly metabolized by diamine oxidase (DAO) and histamine-N-methyltransferase (HNMT). DAO acts mainly in the extracellular space, while HNMT acts intracellularly. Deficiencies in DAO or excessive dietary histamine can contribute to histamine intolerance in some individuals.

Clinically, histamine is implicated in allergic reactions, urticaria, and anaphylaxis, as well as gastric disorders. Antihistamines, especially H1 blockers, reduce allergy symptoms; H2 blockers are used to suppress gastric acid secretion. Treatments may also target histamine release or dietary sources of histamine.