Organic compound found in nearly all animal tissues, in microorganisms, and in some plants. Its release stimulates many smooth muscles to contract, such as those in the gastrointestinal tract, uterus, and the bronchi. It causes fine blood vessels to dilate and become more permeable, causing the runny nose, watery eyes, and tissue swelling of hay fever and some other allergies. Histamine appears to have a physiological role in the body's defenses against a hostile environment, since it may be released when the body is subjected to trauma, infection, or some drugs. Under extreme circumstances, the effects of histamine lead to exaggerated responses with distressing results, as may occur in some allergic conditions (see anaphylaxis). Stinging nettles and certain insect venoms contain histamine. In humans, histamine is formed by removal of a carboxyl group from histidine. Its effects are counteracted by antihistamines.
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Histamine is a biogenic amine involved in local immune responses as well as regulating physiological function in the gut and acting as a neurotransmitter. It is found in virtually all animal body cells. New evidence also indicates that histamine plays an important role in chemotaxis of white blood cells.
Histamine forms colorless hygroscopic crystals that melt at 84°C, and are easily dissolved in water or ethanol, but not in ether. In aqueous solution histamine exists in two tautomeric forms, Nπ-H-histamine und Nτ-H-histamine.
Once formed, histamine is either stored or rapidly inactivated. Histamine released into the synapses is broken down by acetaldehyde dehydrogenase. It is the deficiency of this enzyme that triggers an allergic reaction as histamines pool in the synapses. Histamine is broken down by histamine-N-methyltransferase and diamine oxidase. Some forms of foodborne disease, so-called "food poisonings," are due to conversion of histidine into histamine in spoiled food, such as fish.
Most histamine in the body is generated in granules in mast cells (see figure) or in white blood cells called 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 and alkaloids, including such drugs as morphine, and curare alkaloids, can displace histamine in granules and cause its release. Antibiotics like polymyxin are also found to be stimulating histamine release.
|H1 histamine receptor||Found on smooth muscle, endothelium, and central nervous system tissue||Causes vasodilation, bronchoconstriction, smooth muscle activation, separation of endothelial cells (responsible for hives), and pain and itching due to insect stings; the primary receptors involved in allergic rhinitis symptoms and motion sickness.|
|H2 histamine receptor||Located on parietal cells||Primarily stimulate gastric acid secretion|
|H3 histamine receptor||-||Decreased neurotransmitter release: histamine, acetylcholine, norepinephrine, serotonin|
|H4 histamine receptor||Found primarily in the basophils and in the bone marrow. It is also found on thymus, small intestine, spleen, and colon.||Unknown physiological role.|
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 NREM (non-REM) sleep. Histaminergic cells can be recorded firing just before an animal shows signs of waking.