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Histamine
IUPAC name	2-(1H-imidazol-4-yl)ethanamine
Identifiers
CAS number	51-45-6 Y
PubChem	774
MeSH	Histamine
SMILES	C1=C(NC=N1)CCN
ChemSpider ID	753
Properties
Molecular formula	C5H9N3
Molar mass	111.15 g mol−1
Melting point	83.5 °C (182.3 °F)
Boiling point	209.5 °C (409.1 °F)
Y (what is this?)  (verify) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

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] Histamine triggers the inflammatory response. As part of an immune response to foreign pathogens, histamine is produced by basophils and by mast cells found in nearby connective tissues. Histamine increases the permeability of the capillaries to white blood cells and other proteins, in order to allow them to engage foreign invaders in the affected tissues.^[2] It is found in virtually all animal body cells.^{[citation needed]}

[edit] Properties

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, N^π-H-histamine and N^τ-H-histamine.

Tautomers of histamine

Histamine has two basic centres, namely the aliphatic amino group and whichever nitrogen atom of the imidazole ring does not already have a proton. Under physiological conditions, the aliphatic amino group (having a pK_a around 9.4) will be protonated, whereas the second nitrogen of the imidazole ring (pK_a ≈ 5.8) will not be protonated.^[3] Thus, histamine is normally protonated to a singly-charged cation.

[edit] 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.

Conversion of histidine to histamine by histidine decarboxylase

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.

[edit] Storage and release

Mast cells.

Most histamine in the body is generated in granules in mast cells 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 stimulate histamine release.

[edit] 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.

[edit] Roles in the body

[edit] 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 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.

[edit] Suppressive effects

While histamine has stimulatory effects upon neurons, it also has suppressive ones that protects against the susceptibility to convulsion, drug sensitization, denervation supersensitivity, ischemic lesions and stress.^[4] It has also been suggested that histamine controls the mechanisms by which memories and learning are forgotten.^[5]

[edit] Erection and sexual function

Libido loss and erectile failure can occur following histamine (H2) antagonists such as cimetidine and ranitidine.^[6] The injection of histamine into the corpus cavernosum in men with psychogenic impotence produces full or partial erections in 74% of them.^[7] It has been suggested that H2 antagonists may cause sexual difficulties by reducing the uptake of testosterone.^[6]

[edit] Schizophrenia

Metabolites of histamine metabolite are increased in the cerebrospinal fluid of schizophrenics while the binding of H(1) receptor binding sites are decreased. Many atypical antipsychotics have the effect of increasing histamine turnover.^[8]

[edit] Disorders

As an integral part of the immune system, histamine may be involved in immune system disorders and allergies.

[edit] 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.

[edit] See also

• Scombroid food poisoning
• Histamine antagonist

[edit] References

Histamine and Histamine intolerance[1]

1. ^ Marieb, E. (2001). Human anatomy & physiology. San Francisco: Benjamin Cummings. pp. 414. ISBN 0-8053-4989-8. 
2. ^ Di Guiseppe, Maurice; et al. (2003). Nelson Biology 12. Toronto: Thomson Canada Ltd.. p. 473. ISBN 0-17-625987-2. 
3. ^ Paiva T.B., Tominaga M. & Paiva A.C. (1970). Ionization of histamine, N-acetylhistamine, and their iodinated derivatives. J. Med. Chem., 13, 689–692.
4. ^ Yanai K, Tashiro M. (2007). The physiological and pathophysiological roles of neuronal histamine: an insight from human positron emission tomography studies. Pharmacol Ther. 113(1):1-15. PMID 16890992
5. ^ Alvarez EO. (2009). The role of histamine on cognition. Behav Brain Res. 199(2):183-9. PMID 19126417
6. ^ ^{a b} White JM, Rumbold GR. (1988).Behavioural effects of histamine and its antagonists: a review. Psychopharmacology, 95(1):1-14. PMID 3133686
7. ^ Cará AM, Lopes-Martins RA, Antunes E, Nahoum CR, De Nucci G. (1995). The role of histamine in human penile erection. Br J Urol. 75(2):220-4. PMID 7850330
8. ^ Ito C. (2004). The role of the central histaminergic system on schizophrenia. Drug News Perspect. 17(6):383-7. PMID 15334189

[edit] External links

• DrugBank EXPT01785