Histamine plays a major role in the immune response for allergies, as well as various other purposes in other body systems. The compound is intrinsic to at least 23 physiological functions. Histamine can perform these functions because it has unique chemical properties that allow its versatility in binding. The body can synthesize histamine in all tissues, but the lungs, skin, and gastrointestinal tract have the most histamine.

Histamine Synthesis

Histamine is a small molecule that results from the decarboxylation of histidine. Decarboxylation is a complex chemical reaction that removes a carboxyl group and, as a result, releases carbon dioxide. Carboxyl groups are common and present in many molecules, such as fatty and amino acids. Once the histamine forms, the body either stores it or rapidly inactivates it. Some bacteria are also capable of producing histamine, causing non-infectious foodborne diseases. A similar reaction causes certain fermented foods and drinks, such as wine, to have small amounts of histamine.

wine fermented drinks histamine wundervisuals / Getty Images


Mast Cells

Many immune cells can create histamine, but the most prominent source is mast cells, which exist throughout the body’s connective tissues, performing many important functions. Each mast cell has surface receptors that bind to immunoglobulin E. When an antigen crosslinks immunoglobulin E on the mast cell surface, the cell begins to secrete histamine and other mediators.

mast cell histamine luismmolina / Getty Images


Histamine vs. Allergic Diseases

One of the most widely understood functions of histamine is the mediation of allergic reactions. Researchers believe that the allergic process has two phases: early and late. Within seconds or minutes of allergen exposure, the body releases histamines. This begins the early phase of an allergic response. Different areas of the body have different histamine receptor proteins. Depending on which receptor proteins histamine interacts with, a variety of allergic and inflammatory responses can occur.

allergies allergic response bluecinema / Getty Images


Histamine Receptors

Four histamine receptors are present across different cell types. Each works through different signaling mechanisms, which is why histamine has such diverse effects.

  • H1 appears in smooth muscles and endothelial cells, such as those that line the interior surface of blood vessels. It is responsible for acute allergic responses.
  • H2 appears in the gastric parietal cells in the stomach and plays a role in the secretion of gastric acid.
  • H3 is present in the cells of the central nervous system and helps modulate neurotransmission.
  • H4 appears in mast cells, T cells, dendritic cells, and eosinophils. Its purpose is regulating immune responses.

histamine receptor diagram ttsz / Getty Images


Itching Response

Many irritations can cause an itch, such as insect bites, illness, allergies, and dry skin. Itching is an important reflex that prompts an animal to remove parasites from its skin. In most cases, histamine is responsible for triggering the itch. In some ways, this is an immune response. The H1 receptor is responsible for this process. It’s important to note that not all itches are due to histamine; even minor actions, such as hair touching the skin, can cause an itch.

itch response swelling histamine HeikeKampe / Getty Images



For more than 100 years, doctors have known that injecting histamine causes blood pressure to fall. Histamine binds to endothelial cells and triggers contractions. At the same time, histamine also stimulates the creation and release of many smooth muscle cell relaxants. These functions together cause blood vessel dilation and lower blood pressure. These mechanisms are also important in the processes that lead to anaphylaxis, a severe allergic reaction.

blood pressure vasodilation PeopleImages / Getty Images


Gastric Acid

Within the stomach are gastric glands that contain special cells. These cells, enterochromaffin cells, release histamine that then interacts with the nearby parietal cells by binding to the H2 receptors. The parietal cells then secrete an abundance of hydrochloric acid. Notably, in cases where a person has issues with gastric acid secretion, doctors can prescribe medications that block the effects and functions of the H2 receptors. This dramatically suppresses gastric acid production.

stomach gastric acid Tharakorn / Getty Images


Smooth Muscle Contraction

The human body has several types of muscles. Smooth muscle is non-striated and performs involuntary movements. This type of muscle exists in the walls of hollow organs like the stomach, intestines, and uterus. It also lines the walls of passageways such as the arteries and veins. Histamine can stimulate smooth muscle and cause it to contract. Depending on the location of the muscle, this can have a variety of effects. For example, if a person inhales an allergen, histamine can bind to the H2 receptor and cause bronchodilation, increasing airflow to the lungs.

lung airflow bronchodilation Jan-Otto / Getty Images


Sexual Function

Some people experience erectile failure and a loss of libido when they are taking medications that affect the H2 receptors. Some men have psychogenic impotence, meaning that their erectile failure stems from a psychological cause rather than a physical one. An injection of histamine into the corpus cavernosum of the penis in these men produces full or partial erections in over 70% of cases. Some doctors suggest medication that affects the H2 receptors causes sexual difficulties by preventing testosterone from binding correctly. Regardless, the studies show that histamine plays at least a minor role in human penile erection.

male doctor patient Morsa Images / Getty Images


Sleep-Wake Regulation

Histamine is a neurotransmitter for many of the body’s organs. The brain has a histamine system that transmits throughout the organ. Histamine neurons in this system play a role in the sleep-wake cycle and can cause a person to wake if something activates them. Additionally, these neurons fire rapidly when one is awake, but they slow down when a person experiences tiredness or relaxation. During both REM and NREM sleep, these histamine neurons stop firing entirely. A medication that inhibits H1 receptor function often produces drowsiness because the histamines are not able to promote arousal.

histamine arousal sleep wake Milan_Jovic / Getty Images


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