Histamine

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Histamine

Histamine is a biogenic amine

Biogenic amine

A biogenic amine is a biogenic substance with an amine group....
involved in local immune responses

Immune system

An immune system is a collection of biological processes within an organism that protects against disease by identifying and killing pathogens and tumour cells....
as well as regulating physiological function in the gut and acting as a neurotransmitter

Neurotransmitter

Neurotransmitters are chemistry which relay, amplify and modulate signals between a neuron and another cell . Neurotransmitters are packaged into vesicles that cluster beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to receptors in the membrane on the postsynaptic side of...
. As part of an immune response to foreign pathogens, histamine is produced by basophils and by mast cell

Mast cell

A mast cell is a resident cell of several types of tissues and contains many Granule rich in histamine and heparin. Although best known for their role in allergy and anaphylaxis, mast cells play an important protective role as well, being intimately involved in wound healing and defense against pathogens....
s 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.

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Encyclopedia

Histamine is a biogenic amine

Biogenic amine

A biogenic amine is a biogenic substance with an amine group....
involved in local immune responses

Immune system

Neurotransmitter

Mast cell

Properties

Histamine forms colorless hygroscopic crystal

Crystal

A crystal or crystalline solid is a solid material whose constituent atoms, molecules, or ions are arranged in an orderly repeating pattern extending in all three spatial dimensions....
s that melt at 84°C, and are easily dissolved in water

Water

Water is a common chemical substance that is essential for the survival of all known forms of life. In typical usage, water refers only to its liquid form or States of matter, but the substance also has a solid state, ice, and a gaseous state, water vapor or steam....
or ethanol

Ethanol

Ethanol, also called ethyl alcohol, pure alcohol, grain alcohol, or drinking alcohol, is a volatility , flammable, colorless liquid....
, but not in ether

Diethyl ether

Diethyl ether, also known as ether and ethoxyethane, is a clear, colorless, and highly flammable liquid with a low boiling point and a characteristic odor....
. In aqueous solution

Aqueous solution

An aqueous solution is a solution in which the solvent is water. It is usually shown in chemical equations by appending to the relevant formula....
histamine exists in two tautomer

Tautomer

Tautomers are isomers of organic compounds that readily interconvert by a chemical reaction called tautomerization. Commonly this reaction results in the formal migration of a hydrogen atom or proton, accompanied by a switch of a single bond and adjacent double bond....
ic forms, N^p-H-histamine and N^t-H-histamine.

Histamine has two basic

Base (chemistry)

In chemistry, a base is most commonly thought of as an aqueous substance that can accept protons. A base is also often referred to as an alkali if OH- ions are involved....
centres, namely the aliphatic amino group and whichever nitrogen

Nitrogen

Nitrogen is a chemical element that has the symbol N and atomic number 7 and atomic mass 14.00674?. Elemental nitrogen is a colorless, odorless, tasteless and mostly inert diatomic gas at standard conditions, constituting 78% by volume of Earth's atmosphere....
atom of the imidazole

Imidazole

Imidazole is a organic compound with the formula C3H4N2. This aromatic heterocyclic is classified as an alkaloid....
ring does not already have a proton

Hydrogen

Hydrogen is the chemical element with atomic number 1. It is represented by the chemical symbol H. At standard temperature and pressure, hydrogen is a colorless, odorless, nonmetallic, tasteless, highly combustion and explosive Diatomic molecule gas with the molecular formula H2....
. Under physiological conditions, the aliphatic amino group (having a pK

Dissociation constant

In chemistry and biochemistry, a dissociation constant is a specific type of equilibrium constant that measures the propensity of a larger object to separate reversibly into smaller components, as...
_a around 9.4) will be protonated, whereas the second nitrogen of the imidazole ring (pK_a ˜ 5.8) will not be protonated. Thus, histamine is normally protonated to a singly-charged cation.

Synthesis and metabolism

Histamine is derived from the decarboxylation

Decarboxylation

Decarboxylation is any chemical reaction in which a carboxyl group is split off from a compound as carbon dioxide ....
of the amino acid

Amino acid

In chemistry, an amino acid is a molecule containing both amine and carboxyl functional groups. These molecules are particularly important in biochemistry, where this term refers to alpha-amino acids with the general formula H2NCHRCOOH, where R is an organic substituent....
histidine

Histidine

Histidine is one of the 20 standard amino acids present in proteins. In the nutritional sense, in humans, histidine is considered an essential amino acid, but only in children....
, a reaction catalyzed by the enzyme

Enzyme

Vasoactive

A hormone, drug or chemical which is capable of eliciting vasoconstrictive or vasodilative action on the vasculature. Examples include histamine and heparin, released at the sites of infection which stimulate vasodilation of arterioles and facilaitate an inflammatory response at the site of infection....
amine

Amine

Amines are organic compounds and functional groups that contain a base nitrogen atom with a lone pair. Amines are derivative s of ammonia, wherein one or more hydrogen atoms are replaced by organic substituents such as alkyl and aryl groups....
.

Once formed, histamine is either stored or rapidly inactivated. Histamine released into the synapses is broken down by acetaldehyde dehydrogenase

Acetaldehyde dehydrogenase

Acetaldehyde dehydrogenases are dehydrogenase enzymes which catalyze the conversion of acetaldehyde into acetic acid.The oxidation of acetaldehyde to acetate can be summarized as follows:...
. It is the deficiency of this enzyme

Enzyme

Enzymes are biomolecules that catalysis chemical reactions. Almost all enzymes are proteins. In enzymatic reactions, the molecules at the beginning of the process are called Substrate , and the enzyme converts them into different molecules, the products....
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

Food poisoning

Food poisoning refers to the presentation of acute illness due to the ingestion of food. It can lead to infectious diarrhea.The term usually includes:...
s," are due to conversion of histidine into histamine in spoiled food, such as fish.

Storage and release

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

Brain

The brain is the center of the nervous system in all vertebrate, and most invertebrate, animals. Some primitive animals such as cnidarian and echinoderm have a decentralized nervous system without a brain, while sponges lack any nervous system at all....
, where it functions as a neurotransmitter. Another important site of histamine storage and release is the enterochromaffin-like (ECL) cell

Enterochromaffin-like cell

Enterochromaffin-like cells or ECL cells are a type of neuroendocrine cells found in the gastric glands of the gastric mucosa beneath the epithelium, particularly in the vicinity of parietal cells....
of the stomach

Stomach

In most mammals, the stomach is a hollow muscular organ of the gastrointestinal tract involved in the second phase of digestion, following mastication....
.

The most important pathophysiologic mechanism of mast cell and basophil histamine release is immunologic

Immune system

An immune system is a collection of biological processes within an organism that protects against disease by identifying and killing pathogens and tumour cells....
. These cells, if sensitized by IgE

IGE

IGE is one of the largest MMORPG services companies, with offices in Los Angeles, Miami, and China. IGE is one of the main players in virtual economy services, also known in the MMORPG industry as secondary market....
antibodies

Antibody

Antibodies are gamma globulin proteins that are found in blood or other bodily fluids of vertebrates, and are used by the immune system to identify and neutralize foreign objects, such as bacterium and viruses....
attached to their membranes

Cell membrane

The cell membrane is the interface between the cellular machinery inside the cell and the fluid outside.It is a semipermeable lipid bilayer found in all cell ....
, degranulate

Degranulation

Degranulation is a cellular process that releases antimicrobial cytotoxic molecules from secretion vesicle s called Granule found inside some cells....
when exposed to the appropriate antigen

Antigen

An antigen is a substance that prompts the generation of antibodies and can cause an immune response. The word originated from the notion that they can stimulate antibody generation....
. Certain amine

Amine

Alkaloid

Alkaloids are naturally occurring chemical compounds containing base nitrogen atoms. The name derives from the word alkaline and was used to describe any nitrogen-containing base....
s, including such drugs as morphine

Morphine

Morphine is a highly potent opiate analgesic Medication, is the principal active agent in opium, and is considered to be the prototypical opioid....
, and curare alkaloids, can displace histamine in granules and cause its release. Antibiotic

Antibiotic

In common usage, an antibiotic is a substance or compound that kills or inhibits the growth of bacteria. Antibiotics belong to the group of antimicrobial compounds used to treat infections caused by microorganisms, including fungus and protozoa....
s like polymyxin

Polymyxin

Polymyxins are antibiotics, with a general structure consisting of a cyclicpeptide with a long hydrophobic tail. They disrupt the structure of the...
are also found to be stimulating histamine 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.

Type	Location	Function >- \| H₁ histamine receptor	Found on smooth muscle Smooth muscle Smooth muscle is a type of non-striated muscle, found within the tunica media layer of large and small arteries and veins, the urinary bladder, uterus, male and female reproductive tracts, gastrointestinal tract, respiratory tract, the ciliary muscle, and iris of the eye.... , endothelium Endothelium The endothelium is the thin layer of cell that line the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall.... , and central nervous system Central nervous system The central nervous system is the part of the nervous system that functions to coordinate the activity of all parts of the bodies of multicellular organisms.... tissue	Causes vasodilation Vasodilation Vasodilation refers to the widening of blood vessels resulting from relaxation of smooth muscle cells within the vessel walls, particularly in the large arteries, smaller arterioles and large veins.... , bronchoconstriction Bronchoconstriction Bronchoconstriction is the constriction of the airways in the lungs due to the tightening of surrounding smooth muscle, with consequent coughing, wheezing, and shortness of breath.... , bronchial smooth muscle Smooth muscle Smooth muscle is a type of non-striated muscle, found within the tunica media layer of large and small arteries and veins, the urinary bladder, uterus, male and female reproductive tracts, gastrointestinal tract, respiratory tract, the ciliary muscle, and iris of the eye.... contraction, separation of endothelial cells (responsible for hives), and pain Pain Pain, in the sense of physical pain, is a typical sensory experience that may be described as the unpleasant awareness of a noxious stimulus or bodily harm.... and itching due to insect stings; the primary receptors involved in allergic rhinitis Hay Fever Hay Fever is a comic play written by No?l Coward in 1924 and first produced in 1925 with Marie Tempest as the first Judith Bliss. Best described as a cross between high farce and a comedy of manners, the play is set in an English country house in the 1920s, and deals with the four eccentric members of the Bliss family and their outlandish b... symptoms and motion sickness Motion sickness Motion sickness or kinetosis is a condition in which a disagreement exists between visually perceived movement and the vestibular system's sense of movement.... . \|- \| H₂ histamine receptor	Located on parietal cells	Primarily stimulate gastric acid Gastric acid Gastric acid is one of the main secretions of the stomach, together with several enzymes and intrinsic factor. Chemically it is an acid solution with a pH of 1 to 2 in the stomach lumen , consisting mainly of hydrochloric acid , and large quantities of potassium chloride and sodium chloride .... secretion \|- \| H₃ histamine receptor	-	Decreased neurotransmitter Neurotransmitter Neurotransmitters are chemistry which relay, amplify and modulate signals between a neuron and another cell . Neurotransmitters are packaged into vesicles that cluster beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to receptors in the membrane on the postsynaptic side of... release: histamine, acetylcholine Acetylcholine The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including homo sapiens.... , norepinephrine Norepinephrine Norepinephrine or noradrenaline is a catecholamine with dual roles as a hormone and a neurotransmitter.As a stress hormone, norepinephrine affects parts of the brain where attention and responding actions are controlled.... , serotonin Serotonin Serotonin is a monoamine neurotransmitter synthesized in serotonergic neurons in the central nervous system and enterochromaffin cells in the gastrointestinal tract of animals including humans.... \|- \| H₄ histamine receptor	Found primarily in the basophils and in the bone marrow Bone marrow Bone marrow is the flexible biological tissue found in the hollow interior of bones. In adults, marrow in large bones produces new blood cells.... . It is also found on thymus Thymus In human anatomy, the thymus is an organ located in the upper anterior portion of the Thoracic cavity just behind the sternum. The main function of the thymus is to provide an area for T lymphocyte maturation.... , small intestine Small intestine In vertebrates, including mammals, reptiles, birds, and bony fish, the small intestine is the part of the gastrointestinal tract following the stomach, and is where the vast majority of digestion takes place.... , spleen Spleen The spleen is an organ found in all vertebrate animals. In humans, the spleen is located in the abdomen of the body, where it functions in the destruction of redundant red blood cells, and holds a reservoir of blood.... , and colon Colon (anatomy) The colon is the last portion of the digestive system in most vertebrates; it extracts water and salt from feces before they are defecation from the body.... .	Unknown 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

Hypothalamus

The hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions of the hypothalamus is to link the nervous system to the endocrine system via the pituitary gland ....
, in various tuberomammillary nuclei

Tuberomammillary nucleus

The tuberomammillary nucleus is a subnucleus of the posterior third of the hypothalamus. It consists of, largely, histaminergic and is involved with the control of arousal, sleep and circadian rhythm....
. From here, these histaminergic neurons project throughout the brain, to the cortex

Brain

Medial forebrain bundle

The Medial forebrain bundle , is a complex bundle of axons coming from the basal olfactory regions, the periamygdaloid region, and the septal nuclei, and passing to the lateral hypothalamus, with some carrying on into the tegmentum....
. Histaminergic action is known to modulate sleep

Sleep

Sleep is the natural state of bodily rest observed in humans and other animals. It is common to all mammals and birds, and is also seen in many reptiles, amphibians and fish....
. Classically, antihistamines

Histamine antagonist

A histamine antagonist is an agent which serves to inhibit the release or action of histamine. Antihistamine can be used to describe any histamine antagonist, but it is usually reserved for the H1 antagonist that act upon the histamine H1 receptor....
(H1 histamine receptor antagonists) produce sleep. Likewise, destruction of histamine releasing neurons, or inhibition of histamine synthesis leads to an inability to maintain vigilance

Alertness

Alertness is the state of paying close and continuous attention being watchful and prompt to meet danger or emergency, or being quick to perceive and act....
. 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

NREM

The sleep stages 1 through 3, previously known as stages 1 through 4, are collectively referred to as NREM, non-rapid eye movement, sleep. Rapid eye movement sleep is not included....
(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

Orgasm

An orgasm is the conclusion of the Human sexual response cycle#Plateau phase of Human sexual response cycle, and may be experienced by both males and females....
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

Folic acid

Folic acid and Folate are forms of the water-soluble B vitamins. Vitamin B9 is essential to numerous bodily functions ranging from nucleotide synthesis to the remethylation of homocysteine....
and niacin

Niacin

Niacin, also known as vitamin B3, is a water-soluble vitamin which prevents the Nutrition disorder pellagra. It is an organic compound with the chemical formula C6H5NO2....
(which used in conjunction can increase blood histamine levels and histamine release), or L-histidine.

Schizophrenia

It has been found that about half the patients classified as suffering from schizophrenia

Schizophrenia

Schizophrenia , from the Ancient Greek Root schizein and phren, phren- is a psychiatry diagnosis that describes a mental disorder characterized by abnormalities in the perception or expression of reality....
have low histamine levels in the blood. This may be because of antipsychotics that have unwanted effect on histamine, such as quetiapine

Quetiapine

Quetiapine , marketed by AstraZeneca as Seroquel and by Orion Pharma as Ketipinor, is an atypical antipsychotic used in the management of schizophrenia and bipolar I disorder, and used off-label use for a variety of other purposes, including insomnia and anxiety disorders....
. Although, in these cases, as histamine levels were increased, their health improved.

Disorders

As an integral part of the immune system, histamine 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.

Histamine

Properties

Synthesis and metabolism

Storage and release

Mechanism of action

Roles in the body

Sleep regulation

Sexual response

Schizophrenia

Disorders

Nomenclature

See also

External links