Histamine

Histamine is a small nitrogen-containing molecule, a biogenic amine, made from the amino acid histidine by the enzyme histidine decarboxylase. Most of the body's histamine is stored ready-made in the granules of mast cells and basophils, but cells in the stomach lining and some neurons in the brain also produce it.

When mast cells are triggered, for example by an allergen binding to the IgE on their surface, they release histamine within minutes. It acts on four receptor types, H1 to H4, all of them G protein-coupled receptors. Through H1 receptors it widens small blood vessels and makes them leaky, so fluid seeps into tissue and causes swelling, redness and hives; it also tightens airway muscle and excites nerve endings, causing itch and sneezing. H2 receptors on parietal cells raise stomach acid secretion. H3 receptors work mainly in the nervous system, where histamine helps keep us awake, and H4 receptors on immune cells steer inflammation.

These receptors explain two familiar drug classes. H1 antihistamines such as cetirizine or diphenhydramine ease hay fever and hives, and the older ones cause drowsiness because they enter the brain. H2 blockers such as famotidine lower stomach acid.