Histamine 395877 223764259 2008-07-05T18:02:12Z 168.85.177.4 /* Sexual response */ {{Refimprove|date=January 2008}} {{Chembox new |ImageFile=Histamin - Histamine.svg |ImageSize= |ImageFile2=Histamine3d.png |ImageSize2=200px |IUPACName=2-(3H-imidazol-4-yl)ethanamine |OtherNames= |Section1= {{Chembox Identifiers | CASNo=51-45-6 | PubChem=774 | SMILES=C1=C(NC=N1)CCN | MeSHName=Histamine }} |Section2= {{Chembox Properties | Formula=C<sub>5</sub>H<sub>9</sub>N<sub>3</sub> | MolarMass=111.145 | Appearance= | Density= | MeltingPt= 83.5 °C (182.3 °F) | BoilingPt= 209.5 °C (409.1 °F) | pK<sub>imidasole</sub> 6.04 | pK<sub>NH2</sub> 9.75 | Solubility= }} |Section3= {{Chembox Hazards | MainHazards= | FlashPt= | Autoignition= }} }} '''Histamine''' is a [[biogenic amine]] involved in local [[immune system|immune responses]] as well as regulating physiological function in the gut and acting as a [[neurotransmitter]].<ref>{{tte book |author=Marieb, E. |title=Human anatomy & physiology |publisher=Benjamin Cummings |location=San Francisco |year=2001 |pages=414 |isbn=0-8053-4989-8 |oclc= |doi=}}</ref> It is found in virtually all animal body cells. New evidence also indicates that histamine plays an important role in [[chemotaxis]] of [[white blood cell]]s.{{Fact|date=November 2007}} ==Synthesis and metabolism== Histamine is derived from the [[decarboxylation]] of the [[amino acid]] [[histidine]], a reaction [[catalyst|catalyzed]] by the [[enzyme]] [[L-histidine decarboxylase]]. It is a [[hydrophilic]] [[vasoactive]] [[amine]]. [[Image:Histidine decarboxylase.svg|thumb|center|433px|Conversion of [[histidine]] to [[histamine]] by [[histidine decarboxylase]]]] Once formed, histamine is either stored or rapidly inactivated. Histamine released into the [[synapse]]s is broken down by [[acetaldehyde dehydrogenase]]. <!-- Sentence makes no sense: 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 foodborne disease, so-called "[[food poisoning]]s," are due to conversion of histidine into histamine in spoiled food, such as fish. ==Storage and release== [[Image:SMCpolyhydroxysmall.jpg|thumb|Mast cells]] 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 cell|enterochromaffin-like (ECL) cell]] of the [[stomach]]. The most important pathophysiologic mechanism of mast cell and basophil histamine release is [[immune system|immunologic]]. These cells, if sensitized by [[IgE]] [[antibody|antibodies]] attached to their [[cell membrane|membranes]], [[degranulation|degranulate]] when exposed to the appropriate [[antigen]]. Certain [[amine]]s, 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. {| class="wikitable" | '''Type''' || '''Location''' || '''Function''' |- | [[Histamine H1 receptor|H<sub>1</sub> 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 [[hay fever|allergic rhinitis]] symptoms and [[motion sickness]]. |- | [[Histamine H2 receptor|H<sub>2</sub> histamine receptor]] || Located on [[parietal cells]] || Primarily stimulate [[gastric acid]] secretion |- | [[Histamine H3 receptor|H<sub>3</sub> histamine receptor]] || - || Decreased [[neurotransmitter]] release: histamine, [[acetylcholine]], [[norepinephrine]], [[serotonin]] |- | [[Histamine H4 receptor|H<sub>4</sub> histamine receptor]] || Found primarily in the [[thymus]], [[small intestine]], [[spleen]], and [[colon (anatomy)|colon]]. It is also found on [[basophil]]s 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 nucleus|tuberomammillary nuclei]]. From here, these histaminergic neurons project throughout the brain, to the [[brain|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 [[Alertness|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 [[Rapid eye movement sleep|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 blood histamine levels may suffer from [[premature ejaculation]]s.(Citation Needed) === Schizophrenia === It has been found that about half the patients classified as suffering from [[schizophrenia]] have low histamine levels in the blood.<ref>[http://www.mentalhealthproject.com/content.asp?id_Content=1026 What is Schizophrenia?]</ref> 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.{{Fact|date=June 2008}} However, as an integral part of the immune system it may be involved in [[immune system disorder]]s 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 == <references/> == External links == * {{DrugBank|EXPT01785}} * {{Autacoids}} [[Category:Biogenic amines]] [[Category:Ethylamines]] [[Category:Imidazoles]] [[Category:Immune system]] [[Category:Vasodilators]] [[ar:هستامين]] [[cs:Histamin]] [[da:Histamin]] [[de:Histamin]] [[es:Histamina]] [[fr:Histamine]] [[it:Istamina]] [[he:היסטמין]] [[lt:Histaminas]] [[nl:Histamine]] [[ja:ヒスタミン]] [[no:Histamin]] [[pl:Histamina]] [[pt:Histamina]] [[ru:Гистамин]] [[sk:Histamín]] [[fi:Histamiini]] [[sv:Histamin]] [[tr:Histamin]] [[vi:Histamine]] [[uk:Гістамін]] [[zh:組織胺]]