O Histamine As A Chemical Messenger

Knowledge of the biodisposition of histamine is important in understanding the involvement of this substance in various pathophysiologies as well as the actions of various li-gands that either enhance or block its actions. Each of the steps in the "life cycle" of histamine represents a potential point for pharmacological intervention.

Biosynthesis and Distribution

Histamine is synthesized in Golgi apparatus of its principal storage cells, mast cells, and basophils.6 Histamine is formed from the naturally occurring amino acid l-hisitidne (S-histidine) via the catalysis of either the pyridoxal phosphate dependent enzyme histidine decarboxylase (HDC, EC 4.1.1.22) or l-aromatic amino acid decarboxylase (l-AAAD) (Fig. 23.4). Substrate specificity is higher for HDC versus l-AAAD. HDC inhibitors (HDCIs) include a-fluoromethylhistidine (FMH), a mechanism-based inhibitor, and certain flavonoids.7 Although useful as pharmo-logic probes, HDCIs have not proved to be useful clinically.

Figure 23.1 • Histamine.

Histamine is found in almost all mammalian tissues in concentrations ranging from 1 to more than 100 ^g/g. Mast cells and histamine are in particularly high concentration in skin and the mucosal cells of the bronchi, intestine, urinary tract, and tissues adjacent to the circulation. It is found in higher concentrations in mammalian cerebrospinal fluid than in plasma and other body fluids.

Storage and Release

Most histamine is biosynthesized and stored as protein complexes in mast cells (complexed with heparin) and basophilic granulocytes (complexed with chondroitin).8,9 Protein-complexed histamine is stored in secretory granules and released by exocytosis in response to a wide variety of immune (antigen and antibody) and nonimmune (bacterial products, xenobiotics, physical effects, and cholinergic effects) stimuli. The release of histamine as one of the mediators of

Figure 23.2 • Histamine tautomers and cations.
Body Detox Made Easy

Body Detox Made Easy

What exactly is a detox routine? Basically a detox routine is an all-natural method of cleansing yourbr body by giving it the time and conditions it needs to rebuild and heal from the damages of daily life and the foods you eat and other substances you intake. There are many different types of known detox routines.

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