ABSTRACT
The monoamine histamine is an important chemical messenger that regulates a wide variety of physiological responses in the brain and peripheral organs. In the central nervous system (CNS) this amine is synthesized in a restricted population of neurons located in the tuberomammillary nucleus of the posterior hypothalamus. These neurons project diffusely to most cerebral areas and have been implicated in various functions of the brain of mammalian species (e.g., sleep/ wakefulness, hormonal secretion, cardiovascular control) (1-3). In various peripheral tissues histamine is stored in mast cells, basophils, enterochromaffin cells, and probably also in specific neurons. In the gastric mucosa, histamine release from enterochromaffin cells stimulates the gastric acid secretion by parietal cells, whereas histamine release after mast cell degranulation leads to various allergic phenomena conditions in skin and airway preparations (3, 4). Initially, research in the histamine field focused completely on the role of histamine in allergic diseases. This intensive research resulted in the development of several potent ‘‘antihistamines’’ (e.g., mepyramine), which were useful in inhibiting many symptoms of allergic disorders. The observation that these ‘‘antihistamines’’ could not antagonize all histamine effects led Ash and Schild in 1966 to hypothesize the existence of at least two distinct receptor subtypes (5). In 1972 this hypothesis became generally accepted, when Black and his co-workers succeeded in synthesizing a series of new compounds (e.g., burimamide), which antagonized the effects of histamine on the stomach and heart (6). These H2-
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receptor antagonists proved to be useful in the therapy of gastric ulcers. The identification of the presynaptic H3-receptor as a new receptor subtype in 1983 by Arrang and colleagues (7) gave rise to a new field of interest. The H3-receptor is now regarded as a general regulatory system and a potential target for new therapeutic interventions (8). The use of genomic databases has recently resulted in the identification of a new histamine receptor, the histamine H4-receptor (8a). In view of its expression profile, this receptor is suggested to be a new target in the regulation of immune function.
