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. Histamine is known to be involved in many physiological functions because of its chemical properties that allow it to be versatile in binding. It is Coulombic (able to carry a charge), conformational, and flexible. This allows it to interact and bind more easily.
Histaminylation Protein histaminylation refers to the
post-translational modification in which histamine is covalently attached to
glutamine residues via transamidation.
Monoaminylation itself refers to the
overall class of post-translational modifications involving monoamines; however, these reactions are further classified by the individual
monoamine reactant they describe (i.e.,
dopaminylation,
serotonylation,
histaminylation). Histaminylation has been reported for both histone and non-histone protein substrates, and thus represents a distinct
neuroepigenetic and
neuroproteomic regulatory mechanism with various implications in health and disease. Recent studies have revealed a critical role for histone histaminylation in regulating core components of the sleep-wake cycle and
circadian rhythm in the brain. Despite its discovery in 2012, research as to the direct links between protein histaminylation and disease has seldom occurred and its functions are still largely unknown. histaminergic neurons of the
posterior hypothalamic tuberomammillary nucleus (TMN), and
stomach cancer cell lines. The underlying mechanism concerns both vascular hyperpermeability and vasodilation. Histamine binding to endothelial cells causes them to contract, thus increasing vascular leak. It also stimulates synthesis and release of various vascular smooth muscle cell relaxants, such as
nitric oxide,
endothelium-derived hyperpolarizing factors and other compounds, resulting in blood vessel dilation. These two mechanisms play a key role in the pathophysiology of
anaphylaxis.
Effects on nasal mucous membrane Increased vascular permeability causes fluid to escape from capillaries into the tissues, which leads to the classic symptoms of washing out a poison: a runny nose and watery eyes. Poisons 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 Sleep-wake regulation Histamine is a
neurotransmitter that is released from histaminergic
neurons which project out of the
mammalian
hypothalamus. The cell bodies of these neurons are located in a portion of the posterior
hypothalamus known as the
tuberomammillary nucleus (TMN). The histamine neurons in this region comprise the
brain's histamine system, which projects widely throughout the brain and includes
axonal projections to the
cortex,
medial forebrain bundle, other hypothalamic nuclei, medial septum, the nucleus of the diagonal band, ventral tegmental area, amygdala, striatum, substantia nigra, hippocampus, thalamus and elsewhere. The histamine neurons in the TMN are involved in regulating the
sleep-wake cycle and promote arousal when activated. The
neural firing rate of histamine neurons in the TMN is strongly
positively correlated with an individual's state of arousal. These neurons fire rapidly during periods of wakefulness, fire more slowly during periods of relaxation/tiredness, and stop firing altogether during
REM and
NREM (non-REM) sleep. First-generation
H1 antihistamines (i.e.,
antagonists of
histamine receptor H1) are capable of crossing the
blood–brain barrier and produce
drowsiness by antagonizing histamine H1 receptors in the tuberomammillary nucleus. The newer class of
second-generation H1 antihistamines do not readily permeate the blood–brain barrier and thus are less likely to cause sedation, although individual reactions, concomitant medications and dosage may increase the likelihood of a sedating effect. In contrast,
histamine H3 receptor antagonists increase wakefulness. Similar to the sedative effect of first-generation H1 antihistamines, an inability to maintain
vigilance can occur from the inhibition of histamine biosynthesis or the loss (i.e., degeneration or destruction) of histamine-releasing neurons in the TMN.
Gastric acid release Enterochromaffin-like cells in the stomach release histamine, stimulating parietal cells via H2 receptors. This triggers carbon dioxide and water uptake from the blood, converted to carbonic acid by carbonic anhydrase. The acid dissociates into hydrogen and bicarbonate ions within the parietal cell. Bicarbonate returns to the bloodstream, while hydrogen ions are pumped into the stomach lumen. Histamine release ceases as stomach pH decreases.
Antagonist molecules, such as
ranitidine or
famotidine, block the H2 receptor and prevent histamine from binding, causing decreased hydrogen ion secretion.
Protective effects 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 Loss of libido and
erectile dysfunction can occur during treatment with histamine H2 receptor antagonists such as
cimetidine,
ranitidine, and
risperidone. The injection of histamine into the
corpus cavernosum in males with psychogenic impotence produces full or partial erections in 74% of them. It has been suggested that H2 antagonists may cause sexual dysfunction by reducing the functional binding of testosterone to its androgen receptors.
Multiple sclerosis Histamine therapy for treatment of
multiple sclerosis is currently being studied. The different H receptors have been known to have different effects on the treatment of this disease. The H1 and H4 receptors, in one study, have been shown to be counterproductive in the treatment of MS. The H1 and H4 receptors are thought to increase permeability in the blood-brain barrier, thus increasing infiltration of unwanted cells in the central nervous system. This can cause inflammation, and MS symptom worsening. The H2 and H3 receptors are thought to be helpful when treating MS patients. Histamine has been shown to help with T-cell differentiation. This is important because in MS, the body's immune system attacks its own myelin sheaths on nerve cells (which causes loss of signaling function and eventual nerve degeneration). By helping T cells to differentiate, the T cells will be less likely to attack the body's own cells, and instead, attack invaders. == Disorders ==