Histamine
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Template:Chembox new Histamine is a biogenic amine involved in local immune responses as well as regulating physiological function in the gut and acting as a neurotransmitter.[1] 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 derived from the decarboxylation of the amino acid histidine, a reaction catalyzed by the enzyme L-histidine decarboxylase. It is a hydrophilic vasoactive amine.
Once formed, histamine is either stored or rapidly inactivated. Histamine released into the synapses is broken down by acetaldehyde dehydrogenase, the same enzyme used in the processing of alcohol and acetaldehyde gas produced during combustion. 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 food poisoning are due to conversion of histidine into histamine in spoiled food, such as fish.
Storage and release
Most tissue histamine is found in granules in mast cells (see figure) 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 such drugs 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.
- 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, 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. It is also found on basophils and in the bone marrow.
Roles in the body
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. 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.
Sexual response
Research has shown that histamine is released as part of the human orgasm from mast cells in the genitals, and the histamine release has been connected to the sex flush among women. If this response is lacking while a woman also has trouble achieving orgasm, this may be a sign of histapenia. In such cases, a doctor may prescribe diet supplements with folic acid and niacin (which used in conjunction can increase blood histamine levels and histamine release), or L-histidine. Conversely, men with high histamine levels may suffer from premature ejaculations.
Schizophrenia
It has been found that about half the patients classified as suffering from schizophrenia have low histamine levels in the blood[citation needed]. This may be because of antipsychotics that have unwanted effect on histamine, such as Quetiapine. Although, in these cases, as histamine levels were increased, their health improved.
Disorders
High or low histamine levels are considered by some of the alternative medicine community to be health issues; this is not accepted by the mainstream medical community. However, as an integral part of the immune system it may be involved in immune system disorders and allergies.
See also
References
- ^ Marieb, E. (2001). Human anatomy & physiology. San Francisco: Benjamin Cummings. p. 414. ISBN 0-8053-4989-8.