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Histamine is an active substance found in a large range of living organisms that plays a major role in allergic reaction, dilating blood vessels and increasing the permeability of vessel walls. It also acts as a neurotransmitter or chemical messenger that carries signals from one nerve to another, as well as performing several other important functions in various bodily tissues.

Histamine is classified as an amine because it is based on the structure of ammonia and is formed through decarboxylation of the amino acid histidine. Histamine is an autacoid, which means it acts similarly to a local hormone, near its site of synthesis. It is produced as part of the local immune response to invading bodies and triggers inflammation.

Histamine exerts its effects by binding to histamine receptors on cells’ surfaces. There are four types of histamine receptor: H1, H2, H3 and H4. The binding of histamine to these receptors stimulates them to produce functional responses and these are described in more detail below:

• The H1 histamine receptor plays an important role in allergic response and is widely distributed throughout the peripheral nervous system, particularly the smooth muscle, where its activation causes vasoconstriction. Activation of the H1 receptor also causes blood vessel dilation, increased vessel permeability, stimulation of sensory nerves in the airways and bronchoconstriction. In addition, activation of this receptor promotes the chemotaxis of eosinophils, which can lead to nasal congestion, sneezing and rhinorrhea. Once activated in the cerebral cortex, the H1 receptor can inhibit potassium channels in neuronal cell membranes, depolarizing the neurons and increasing neuronal excitation.

• The H2 receptor is found on the parietal cells within the stomach, heart and to a limited extent, in immune cells and vascular smooth muscle. Activation of the H2 receptor stimulates vasodilation and release of the gastric acids required for digestion. Physical responses to the H2 receptor include a decrease in the chemotaxis and activation of neutrophils and basophils, stimulation of suppressor T cells, lymphocyte proliferation and natural killer cell activity. Combined activation of H1 and H2 receptors contributes to rhinorrhea and swelling of the nasal airways.

• The H3 histamine receptor is a presynaptic autoreceptor found on nerve cells that contain histamine. It is widely distributed throughout the central nervous system, with the greatest expression found in the cortex, caudate nucleus, thalamus, hypothalamus, olfactory tubercle and hippocampus. The diverse distribution of the H3 receptor throughout the cortex suggests this receptor is able to modulate many neurotransmitters such as dopamine, GABA, acetylcholine and norepinephrine in the central and peripheral nervous systems.

• The H4 histamine receptor is mainly found on immune cells and tissues including peripheral blood leukocytes, the spleen, bone marrow and thymus. It is also found in the colon, lung, liver and epicanthus. Stimulation of this receptor also mediates the chemotaxis of eosinophils and upregulates adehsion of molecules.

Antihistamines

Anithistamines are drugs used to block the activity of histamines, by preventing the ability of histamine to bind to histamine receptors. These agents are therefore referred to as histamine antagonists. The traditional antihistamines that are used to treat allergy block H1 receptors, while H2 antagonists inhibit gastric acid secretion to help treat peptic ulcers. The H4 receptor is a potential target for treating allergic and inflammatory conditions such as asthma and allergic rhinitis. The ability of the H3 receptor to modulate various neurotransmitters makes this receptor a novel therapeutic target in the relief of symptoms caused by several conditions including movement disorders, obesity, schizophrenia, abnormal sleep/wake patterns and ADHD.

Further Reading

• All Histamine Content
• What Does Histamine Do?
• What is Histamine?
• Histamine Storage and Release

Written by

Sally Robertson

Sally has a Bachelor's Degree in Biomedical Sciences (B.Sc.). She is a specialist in reviewing and summarising the latest findings across all areas of medicine covered in major, high-impact, world-leading international medical journals, international press conferences and bulletins from governmental agencies and regulatory bodies. At News-Medical, Sally generates daily news features, life science articles and interview coverage.