Histamine Histamine Jack Hitt Category="Cytokines"Category="Immune system"Category="Monoamines"[image] Histamine is a biogenic Amine chemical involved in local immune responses as well as regulating physiological function in the gut and acting as a neurotransmitter. New evidence also indicates that histamine plays a role in Chemotaxis of white blood cells.

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). Once formed, histamine is either stored or rapidly inactivated. 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.

Storage and Release

Most tissue histamine is found in granules in mast cells or basophils. Mast cells are especially numerous at sites of potential injury - the nose, mouth, and feet; internal body surfaces; and blood vessels. Non-mast cell histamine is found in several tissues, including the brain, where it functions as a neurotransmitter. Another important site of histamine storage and release is the enterochromaffin-like (ECL)cell of the stomach.

The most important pathophysiologic mechanism of mast cell and basophil histamine release is immunologic. These cells, if sensitized by IgE antibodies attached to their membranes, degranulate when exposed to the appropriate Antigen. Certain amines, including drugs such as Morphine and tubocurarine, can displace histamine in granules and cause its release.

Mechanism of Action

Histamine exerts its actions by combining with specific cellular receptors located on cells. The four histamine receptors that have been discovered are designated H1 through H4.

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

References