PHYSIOLOGICAL ROLE OF HISTAMINE
The endogenous biogenic amine histamine is synthesized in the presence of the amino acid L-histidine (Figure 3) . Initially, histamine was recognized as a mediator of allergies. In early 1932, scientists discovered its role in the modulation of allergic reactions. Subsequently, researchers have established that histamine is a mediator of autoimmune conditions, hematopoiesis and gastric acid secretion . Histamine is circulated throughout the tissues and is mainly concentrated the in lungs, skin, gastrointestinal tract, mast cells, basophils, neurons and parietal cells. A large amount of histamine in granules is delivered by basophils and mast cells and is linked with chondroitin-4-sulfate and anionic proteoglycans heparin . The key reason that triggers the histamine is an allergic reaction where B cells are first activated and form plasma cells which release a large amount of antibodies. The activation of IgE triggers the mast cell to release granules rich in histamine (Figure 4) . Histamine-N-methyl transferase which is responsible for the degradation of histamine in epithelial cells of the airway and diamine oxidase present in the liver, kidney, small intestine mucosa, eosinophils, placenta and skin are the two major pathways that metabolized 97% of the synthesized histamine . Histamine part in allergic disease and autoimmune has an important role in numerous pathological and physiological progressions, specifically in chronic urticaria due to histamine release from basophils and circulating IgE antibodies against FcεRIα and IgE . Allergic rhinitis, Atopic dermatitis, allergic rhinitis, anaphylaxis and bronchoconstriction are other examples of allergic and autoimmune diseases . Lately, histamine confirmed as a serious factor in interaction with infiltrating immune cells and tumour tissues, where the mechanism of the immune system containing histamine allows malignant cells to escape. Various in vitro and in vivo studies of human cell lines of cancers such as lymphoma, breast cancer, ovarian cancer, etc. have shown clear participation of histamine in malignant cell proliferation .