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What’s Histamine Doing in Your Body?

A lot. Histamine is a chemical messenger that travels to 1 of 4 types of receptors. Once histamine meets and binds with one of these receptors, it triggers more chemistry, serving many functions throughout the body. Histamine is generated in mast cells, and white blood cells called basophils and eosinophils. Most histamine is found in the skin, lungs and the gastrointestinal tract. It’s best known as a culprit in allergies. Too much histamine does cause problems, but it’s actually an indispensable part of your body chemistry.

H1 Histamine Receptors

Stimulating H1 receptors causes…

  • Acute allergic responses. Excessive stimulation of these receptors can cause hives, broncho-constriction (wheezing and asthma symptoms), and motion sickness. They are also responsible for symptoms of seasonal allergies and hayfever.
  • Non-vascular smooth muscle constriction. This includes intestinal muscle peristalsis (moving food along) and lung airway constriction.[1]
  • Vascular permeability. Smooth muscle in blood vessels also constrict, causing the cell-lining of blood vessels to separate, making them extra permeable. That vascular permeability allows fluid to escape from capillaries into tissues, which is responsible for running noses, skin redness and watery eyes. Classic allergy symptoms.[1]
  • Vasodilation. This is derived from nitric oxide production. Capillaries, your smallest blood vessels, are dilated. This can cause flushing, a drop in blood pressure, and headaches. These affects are said to be fast-acting (compared to H2 induced vasodilation) and tends to disappear relatively quickly.
  • Maintaining your internal clock. These are essential for modulating your circadian rhythm (your internal clock). Histamine stimulating H1 receptors in your brain alters your neurochemistry to make you more awake and alert. This explains why antihistamines cause drowsiness, because they block histamine from binding with H1 receptors.

Symptoms can be counteracted with H1 antihistamines like benadryl and zyrtec. Antihistamines (aka antagonists) work by blocking the receptor site so that histamine can’t bind to trigger them.

H2 Histamine Receptors

H2 receptors are responsible for…

  • Secreting gastric acid. These are found on parietal cells in the stomach lining, and are mainly responsible for regulating the levels of stomach gastric acid. Triggering these receptors stimulates the release of gastric acid. This is essential in digesting your food, but too much can cause problems like heartburn.
  • Regulating immune response. H2 receptors are also found on the most common type of white blood cells called neutrophils. Histamine can also inhibit antibody and cytokine production by reacting with these receptors.[2]
  • Vasodilation. Blood vessels are dilated, and the effect is considered to have a slow onset and to be longer-lasting.

Symptoms can be treated with H2 antihistamines like pepcid and zantac.

Interesting facts

  • Histamine is a suspected agent in pancreatic conditions. H2 antihistamines are used to treat acute pancreatitis. Histamine has been identified as a vasodilator in pancreatitis, but its exact function is under study.[3],[4]
  • Research is still being done to determine how H2 receptors affect other aspects of the body including the heart rate, lung airways, and skin.[5]

H3 Histamine Receptors

  • H3 receptors modulate neurotransmission. They are primarily found in the central nervous system (the brain), and serve as a sort of shut-off valve for the synthesis of more histamine.[9] When these receptors are triggered, they signal to inhibit further histamine production.
  • H3 antagonists have cognitive and stimulant effects, which is why they’re being researched for potential treatment of nervous system disorders like schizophrenia, ADHD and Alzheimer’s.[7],[8]
  • Antihistamines targeting H3 and H4 receptors are still a topic of research, and aren’t over-the-counter medications.[6]

H4 Histamine Receptors

  • H4 receptors regulate immune responses. These receptors regulate the release of white blood cells from bone marrow. They’ve also been shown to direct mast cells, eosinophils, and basophils through what’s called chemotaxis.[9],[10] 
  • H4 receptors are also found in the thymus, small intestine, spleen, colon, and white blood cells.
  • Drug development targeting H4 receptors are promising for potential treatment of inflammatory disorders like asthma, allergic rhinitis, inflammatory bowel disease, and rheumatoid arthritis.[10]

[1] Arrang, J.-M, and Börje Uvnäs. Histamine and Histamine Antagonists. Berlin: Springer-Verlag, 1991. Print.









[10] Golan, David E., April W. Armstrong, and Armen H. Tashjian. Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy. 2nd ed. Philadelphia: Lippincott Williams & Wilkins, 2007. Print.

Some general references


Read about how a low histamine diet could help.

Published in Science-y Stuff


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