Histamine

Histamine is a biogenic amine chemical involved in local immune responses as well at regulating physiological function in the gut and acting as a neurotransmitter.

Synthesis and Metabolism

Chemically, histamine is 2-(4-imidazolyl)ethylamine and has the formula C₅H₉N₃. Histamine is synthesized by the decarboxylation of the amino acid histidine, a reaction catalyzed by the enzyme L-histidine decarboxylase. It is a hydrophilic vasoactive amine (thus the name). Histamine is broken down by histamine-N-methyltransferase and diamine oxidase, and is also possibly taken up by a transporter. Some forms of food poisoning are due to conversion of histidine into histamine in spoiled foodstuffs, such as fish.

Physiology

Release of histamine is associated with allergic reactions, as it causes both an inflammatory response and a contraction of smooth muscle tissue. Histamine is released by mast cells primarily when they degranulate in response to signaling triggered by cell surface receptors, termed FcεRI receptors, that are crosslinked by IgE antibodies binding allergens.

Histamine also regulates gastric acid production. It is released by ECL cells in the stomach to stimulate parietal cells to release HCl.

It also functions as a neurotransmitter in the central nervous system.

Histamine mediates its effects via histamine receptors, which are classified into types:

• H₁ histamine receptor - vasodilation; bronchoconstriction; smooth muscle activation; separation of endothelial cells, responsible for hives; pain and itching due to insect stings; primary receptors involved in allergic rhinitis symptoms and motion sickness
• H₂ histamine receptor - located on parietal cells, which primarily regulate gastric acid secretion
• H₃ histamine receptor - decreased neurotransmitter release: histamine, acetylcholine, norepinephrine, serotonin
• H₄ histamine receptor - unknown physiological role. Found primarily in the thymus, small intestine, spleen, and colon.

Sleep regulation

Histamine is released as a neurotransmitter. The cell bodies of neurons which release histamine are found in the posterior hypothalamus, in various tuberomammillary nuclei. From here, these histaminergic neurons project throughout the brain, to the cortex through the medial forebrain bundle. Histaminergic action is known to modulate sleep. Classically, antihistamines (H1 histamine receptor antagonists) produce sleep. Likewise, destruction of histamine releasing neurons, or inhibition of histamine synthesis leads to an inability to maintain vigilance in novel situations. Finally, H3 receptor antagonists (which stimulate histamine release) increase wakefulness.

It has been shown that histaminergic cells have the most wakefulness-related firing pattern of any neuronal type thus far recorded. They fire rapidly during waking, fire more slowly during periods of relaxation/tiredness and completely stop firing during REM and non-REM sleep. Histaminergic cells can be recorded firing just before an animal shows signs of waking.

See also

• Antihistamine
• Basophil
• Mast cell
• Allergy
• Atopy