Histamine

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.^{[citation needed]}.

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Synthesis and metabolism

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. 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.

Storage and release

  Most histamine in body tissue 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 histamine receptors. The four histamine receptors that have been discovered are designated H1 through H4.

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 NREM (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. If this response is lacking this may be a sign of histapenia (histamine deficiency). 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.^[2] 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.

Nomenclature

"H substance" or "substance H" are occasionally used in medical literature for histamine or a hypothetical histamine-like diffusible substance released in allergic reactions of skin and in the responses of tissue to inflammation.

See also

• Scombroid poisoning

References

1. ^ Marieb, E. (2001). Human anatomy & physiology. San Francisco: Benjamin Cummings, 414. ISBN 0-8053-4989-8. 
2. ^ What is Schizophrenia?