11.04.1 Synthesis, Receptors and Actions

Histamine is found in virtually all tissues in the body. It is synthesised from the precursor amino acid histidine via histidine decarboxylase. Once synthesised it is stored in granules in mast cells, basophils and enterochromafin-like cells in the gastric fundus. It is also synthesised in brain as a neurotransmitter.

Mast and basophil histamine is released in response to exposure to antigens and venoms, and toxins also elicit release of histamine, for example in the insect bites. Histamine released from gastric cells by cholinergic stimulation and by other stimulants (e.g. gastrin) cause gastric acid secretion. Morphine can also cause release of histamine from mast cells and histamine allergic reactions are common with the use of many drugs. Once released, histamine is metabolised quickly and excreted.

Histamine acts on specific histamine receptors, denoted H₁-H₄ which are all G-protein coupled receptors (GPCR). Histamine H₁ receptors are present on smooth muscle (bronchoconstriction, uterine and GIT smooth muscle contraction), endothelium (increase vascular permeability), CNS (motion sickness). Allergic rhinitis is mediated via H₁ receptors, as histamine acting on these receptors causes itching (sensory nerves), mucus secretion (submucosal glands), vasodilatation and oedema (vascular smooth muscle and endothelium).

Histamine H₂ receptors are present on gastric parietal cells (acid secretion) and vascular smooth muscle cells (vasodilatation). Histamine H₃ receptors are found in the central nervous system. Histamine H₄ receptors are found on many cell types and are thought to be involved in chemotaxis.