Histamine H₄ receptors in the gastrointestinal tract.

Histamine is a well-established mediator involved in a variety of physiological and pathophysiological mechanisms and exerts its effect through activation of four histamine receptors (H-1-H-4). The histamine H-4 receptor is the newest member of this histamine receptor family, and is expressed throughout the gastrointestinal tract as well as in the liver, pancreas and bile ducts. Functional studies using a combination of selective and non-selective H-4 receptor ligands have rapidly increased our knowledge of H-4 receptor involvement in gastrointestinal processes both under physiological conditions and in models of disease. Strong evidence points towards a role for H-4 receptors in the modulation of immune-mediated responses in gut inflammation such as in colitis, ischaemia/reperfusion injury, radiation-induced enteropathy and allergic gut reactions. In addition, data have emerged implicating H-4 receptors in gastrointestinal cancerogenesis, sensory signalling, and visceral pain as well as in gastric ulceration. These studies highlight the potential of H-4 receptor targeted therapy in the treatment of various gastrointestinal disorders such as inflammatory bowel disease, irritable bowel syndrome and cancer.