Vasoactive Amines: Histamine and Serotonin in Mediators of Inflammation
المؤلف:
Vinay Kumar, MBBS, MD, FRCPath; Abul K. Abbas, MBBS; Jon C. Aster, MD, PhD
المصدر:
Robbins & Cotran Pathologic Basis of Disease
الجزء والصفحة:
10th E ,P83
2025-11-08
56
The two major vasoactive amines, so named because they have important actions on blood vessels, are histamine and serotonin. They are stored as preformed molecules in cells and are therefore among the first mediators to be released during inflammation. The richest sources of histamine are the mast cells that are normally present in the connective tissue adjacent to blood vessels. It is also found in blood basophils and platelets. Histamine is stored in mast cell granules and is released by mast cell degranulation in response to a variety of stimuli, including (1) physical injury, such as trauma, cold, or heat, by unknown mechanisms; (2) binding of antibodies to mast cells, which underlies immediate hypersensitivity (allergic) reactions (Chapter 6); and (3) products of complement called anaphylatoxins (C3a and C5a), described later. Antibodies and complement products bind to specific receptors on mast cells and trigger signaling pathways that induce rapid degranulation. In addition, leukocytes are thought to secrete some histamine-releasing proteins but these have not been characterized. Neuropeptides (e.g., substance P) and cytokines (IL-1, IL-8) may also trigger release of histamine.
Histamine causes dilation of arterioles and increases the permeability of venules. Histamine is considered to be the principal mediator of the immediate transient phase of increased vascular permeability, producing interendothelial gaps in venules, as discussed earlier. Its vasoactive effects are mediated mainly via binding to receptors, called H1 receptors, on microvascular endothelial cells. The antihistamine drugs that are commonly used to treat some inflammatory reactions, such as allergies, are H1 receptor antagonists that bind to and block the receptor. Histamine also causes contraction of some smooth muscles.
Serotonin (5-hydroxytryptamine) is a preformed vasoactive mediator present in platelets and certain neuroendocrine cells, such as in the gastrointestinal tract, and in mast cells in rodents but not humans. Its primary function is as a neurotransmitter in the gastrointestinal tract. It is also a vasoconstrictor, but the importance of this action in inflammation is unclear.
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