Histamine, [2-(imidazol-4-y1) ethylamine], which is biosynthesized by decarboxylation of the basic amino acid histidine, is found in all organs and tissues of the human body.
The histamine is stored in the secretory granules of mast cells (pH 5.5) as positively charged and ionically complexed with negatively charged acidic group on other seceretory granules, which constitutes heparin. The principal target cells of immediate hypersensitivity reactions are mast cells and basophils to generate
IgE antibodies that binds to FC€ receptor on the granule surface. This leads to transmembrane activation of tyrosine protein kinase, which phosphorylates and activates the phospolipase. The phosphotidyl inositol biphosphate is converted into inositol triphosphate, which triggers the intracellular release of calcium ion.
The calcium ion causes exocytic release of histamine with the transfer of Na+ ion from extracellular space. The released histamine targets the histaminergic receptors (H1, H2, and H3) to elicit the actions.
Histamine is an important chemical messenger, communicating information from one cell to another, and is involved in a variety of complex biological actions. It is mainly stored in an inactive bound form, from which it is released as a result of an antigen–antibody reaction, initiated by different stimuli, such as venoms, toxins, proteolytic enzyme, detergents, food materials, and numerous chemicals. Systemically, histamine contracts smooth muscles of the lungs and the gastrointestinal system and cause vasodialation, low blood pressure, and increases the heart rate. It also causes symptoms such as itching, sneezing, watery eye, and running nose.
Histamine exerts its biological function by interacting with at least three distinctly specifi c receptors H1, H2, and H3. Historically, the term antihistamine has been used to describe a drug that acts on H1 and H2 receptors. An antihistaminic agent should ideally prevent the production or release of these autocoids by inhibiting the response of sensitized mast cells and basophils to specifi c antigens.
1. Antihistamines are drugs that competitively blocks the H1 receptors.
2. Antihistamines antagonize the stimulant action of histamine on the smooth muscles of gastro intestinal tract (GIT), uterus, and blood vessels, and inhibit histamine augmented salivary secretion.
3. H1-receptor antagonists have been used clinically to treat various allergic disorders, such as seasonal or perennial allergic rhinitis and chronic urticaria.
Release and Function of Endogenous Histamine Histamine is released because of the interaction of an antigen with IgE antibodies on the mast cell surface and plays a central role in immediate hypersensitive reactions