Most histamine in the body is generated in granules in mast cells or in white blood cells called basophils. Mast cells are especially numerous at sites of potential injury - the nose, mouth, and feet, internal body surfaces, and blood vessels.
Non-mast cell histamine is found in several tissues, including the brain, where it functions as a neurotransmitter.
Another important site of histamine storage and release is the enterochromaffin-like (ECL) cell of the stomach.
The most important pathophysiologic mechanism of mast cell and basophil histamine release is immunologic. These cells, if sensitized by IgE antibodies attached to their membranes, degranulate when exposed to the appropriate antigen.
Certain amines and alkaloids, including such drugs as morphine, and curare alkaloids, can displace histamine in granules and cause its release.
Antibiotics like polymyxin are also found to stimulate histamine release.
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