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
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 receptors
located on cells. The four histamine receptors that have been discovered are designated H1 through H4.
| Type |
Location |
Function |
| 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 regulate gastric acid secretion |
| H3 histamine receptor |
- |
Decreased neurotransmitter release: histamine, acetylcholine, norepinephrine, serotonin |
| H4 histamine receptor |
Found primarily in the thymus, small intestine,
spleen, and colon. It is also found on basophils and in the bone marrow. |
Unknown physiological role. |
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
References
- ^ Marieb, E. (2001). Human
anatomy & physiology. San Francisco: Benjamin Cummings, 414. ISBN 0-8053-4989-8.
- ^ What is Schizophrenia?
External links
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