HISTAMINE is an organic nitrogenous compound involved in local immune
responses as well as regulating physiological function in the gut and
acting as a neurotransmitter for the uterus.
* 1 Properties * 2 Synthesis and metabolism * 3 Storage and release * 4 Mechanism of action
* 5 Roles in the body
Vasodilation and a fall in blood pressure
* 5.2 Effects on nasal mucous membrane
* 5.3 Sleep-wake regulation
* 6 Disorders * 7 History * 8 See also * 9 References * 10 External links
SYNTHESIS AND METABOLISM
Once formed, histamine is either stored or rapidly inactivated by its primary degradative enzymes , histamine-N-methyltransferase or diamine oxidase . In the central nervous system, histamine released into the synapses is primarily broken down by histamine-N-methyltransferase , while in other tissues both enzymes may play a role. Several other enzymes, including MAO-B and ALDH2 , further process the immediate metabolites of histamine for excretion or recycling.
Bacteria also are capable of producing histamine using histidine
decarboxylase enzymes unrelated to those found in animals. A
non-infectious form of foodborne disease, scombroid poisoning , is due
to histamine production by bacteria in spoiled food, particularly
fish. Fermented foods and beverages naturally contain small quantities
of histamine due to a similar conversion performed by fermenting
bacteria or yeasts.
STORAGE AND RELEASE
Most histamine in the body is generated in granules in mast cells and
in white blood cells (leukocytes) called basophils and eosinophils .
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.
MECHANISM OF ACTION
In humans, histamine exerts its effects primarily by binding to G protein-coupled histamine receptors , designated H1 through H4. As of 2015, histamine is believed to activate ligand-gated chloride channels in the brain and intestinal epithelium.
TYPE LOCATION FUNCTION SOURCE
* CNS: Produced in the histaminergic tuberomammillary nucleus , projecting to the dorsal raphe , locus coeruleus , and additional structures. * PERIPHERY: Smooth muscle , endothelium , sensory nerves
* CNS: Sleep-wake cycle (promotes wakefulness), body temperature , nociception , endocrine homeostasis , regulates appetite , involved in cognition * PERIPHERY: Causes bronchoconstriction , bronchial smooth muscle contraction, vasodilation , promotes hypernociception (visceral hypersensitivity ), involved in itch perception and urticaria .
* CNS: Dorsal striatum (caudate nucleus and putamen ), cerebral cortex (external layers), hippocampal formation , dentate nucleus of the cerebellum (note: almost all known H2 receptor antagonists e.g., ranitidine, famotidine) * PERIPHERY: Located on parietal cells , vascular smooth muscle cells , neutrophils , mast cells , as well as on cells in the heart and uterus
* CNS: Not established (note: most known H2 receptor ligands are unable to cross the blood–brain barrier in sufficient concentrations to allow for neuropsychological and behavioral testing) * PERIPHERY: Primarily involved in vasodilation and stimulation of gastric acid secretion. Modulates gastrointestinal function.
Histamine H3 receptor Found on central nervous system and to a lesser extent peripheral nervous system tissue Autoreceptor and heteroreceptor functions: decreased neurotransmitter release of histamine, acetylcholine , norepinephrine , serotonin Modulates nociception, gastric acid secretion, and food intake.
Histamine H4 receptor Found primarily in the basophils and in the bone marrow . It is also found on thymus , small intestine , spleen , and colon . Plays a role in mast cell chemotaxis , itch perception, cytokine production and secretion, and visceral hypersensitivity. Other functions (inflammation, allergy, cognition, etc.) have not been fully characterized.
Histamine-gated chloride channel Putatively: CNS (hypothalamus, thalamus) and intestinal epithelium Brain: Produces fast inhibitory postsynaptic potentials Intestinal epithelium: chloride secretion (associated with secretory diarrhea )
ROLES IN THE BODY
Although histamine is small compared to other biological molecules
(containing only 17 atoms), it plays an important role in the body. It
is known to be involved in 23 different physiological functions.
VASODILATION AND A FALL IN BLOOD PRESSURE
When injected intravenously, histamine causes most blood vessels to dilate, and hence causes a fall in the blood pressure. This is a key mechanism in anaphylaxis , and is thought to be caused when histamine releases nitric oxide , endothelium-derived hyperpolarizing factors and other compounds from the endothelial cells.
EFFECTS ON NASAL MUCOUS MEMBRANE
Increased vascular permeability causes fluid to escape from capillaries into the tissues, which leads to the classic symptoms of an allergic reaction: a runny nose and watery eyes. Allergens can bind to IgE -loaded mast cells in the nasal cavity 's mucous membranes . This can lead to three clinical responses:
* sneezing due to histamine-associated sensory neural stimulation * hyper-secretion from glandular tissue * nasal congestion due to vascular engorgement associated with vasodilation and increased capillary permeability
Histaminergic neurons have a wakefulness-related firing pattern. They fire rapidly during waking, fire more slowly during periods of relaxation/tiredness and completely stop firing during REM and NREM (non-REM) sleep.
GASTRIC ACID RELEASE
Enterochromaffin-like cells , located within the gastric glands of
the stomach, release histamine that stimulates nearby parietal cells
by binding to the apical H2 receptor. Stimulation of the parietal cell
induces the uptake of carbon dioxide and water from the blood, which
is then converted to carbonic acid by the enzyme carbonic anhydrase.
Inside the cytoplasm of the parietal cell, the carbonic acid readily
dissociates into hydrogen and bicarbonate ions. The bicarbonate ions
diffuse back through the basilar membrane and into the bloodstream,
while the hydrogen ions are pumped into the lumen of the stomach via a
K+/H+ ATPase pump .
While histamine has stimulatory effects upon neurons, it also has suppressive ones that protect against the susceptibility to convulsion , drug sensitization, denervation supersensitivity , ischemic lesions and stress. It has also been suggested that histamine controls the mechanisms by which memories and learning are forgotten.
ERECTION AND SEXUAL FUNCTION
Libido loss and erectile failure can occur during treatment with histamine H2 receptor antagonists such as cimetidine , ranitidine , and risperidone . The injection of histamine into the corpus cavernosum in men with psychogenic impotence produces full or partial erections in 74% of them. It has been suggested that H2 antagonists may cause sexual difficulties by reducing the uptake of testosterone.
Metabolites of histamine are increased in the cerebrospinal fluid of people with schizophrenia , while the efficiency of H1 receptor binding sites is decreased. Many atypical antipsychotic medications have the effect of increasing histamine production, because histamine levels seem to be imbalanced in people with that disorder.
As an integral part of the immune system, histamine may be involved
in immune system disorders and allergies .
The properties of histamine, then called β-iminazolylethylamine, were first described in 1910 by the British scientists Henry H. Dale and P.P. Laidlaw . By 1913 the name histamine was in use, using combining forms of histo- + amine , yielding "tissue amine".
"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.
* Scombroid food poisoning * H1 receptor antagonist * Hay fever (allergic rhinitis)
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