Roles in the body[edit]

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 so many physiological functions because of its chemical properties that allow it to be so versatile in binding. It is Coulombic (able to carry a charge), conformational, and flexible. This allows it to interact and bind more easily.[6]

Sleep-wake regulation[edit]

Histamine is released as a neurotransmitter. The cell bodies of histamine neurons are found in the posterior hypothalamus, in the tuberomammillary nuclei. From here, these neurons project throughout the brain, including to the cortex, through the medial forebrain bundle. Histamine neurons increase wakefulness and prevent sleep.[13] Classically, antihistamines (H1 histamine receptor antagonists) which cross the blood-brain barrier produce drowsiness. Newer antihistamines are designed to not cross into the brain and so do not have this effect. Similar to the effect of older antihistamines, destruction of histamine releasing neurons, or inhibition of histamine synthesis leads to an inability to maintain vigilance. Finally, H3 receptor antagonists increase wakefulness.

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[edit]

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. Histamine release is halted when the pH of the stomach starts to decrease. Antagonist molecules, like ranitidine, block the H2 receptor and prevent histamine from binding, causing decreased hydrogen ion secretion.

Protective effects[edit]

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.[14] It has also been suggested that histamine controls the mechanisms by which memories and learning are forgotten.[15]

Erection and sexual function[edit]

Libido loss and erectile failure can occur during treatment while using of histamine (H2) receptor antagonists such as cimetidine, ranitidine, and risperidone.[16] The injection of histamine into the corpus cavernosum in men with psychogenic impotence produces full or partial erections in 74% of them.[17] It has been suggested that H2 antagonists may cause sexual difficulties by reducing the uptake[clarification needed] of testosterone.[16]

Schizophrenia[edit]

Metabolites of histamine are increased in the cerebrospinal fluid of people with schizophrenia, while the efficiency of H(1) receptor binding sites is decreased. Many atypical antipsychotic medications have the effect of decreasing histamine production (antagonist), because its use seems to be imbalanced in people with that disorder.[18]

Multiple sclerosis[edit]

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.[19]

Disorders[edit]

As an integral part of the immune system, histamine may be involved in immune system disorders[citation needed] and allergies. Mastocytosis is a rare disease in which there is a proliferation of mast cells that produce excess histamine.[20]

History[edit]

The properties of histamine, then called β-iminazolylethylamine, were first described in 1910 by the British scientists Henry H. Dale and P.P. Laidlaw.[21]

“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.[citation needed]

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