Histamine<scp>H</scp>₄receptors in the gastrointestinal tract

<jats:p>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 (<jats:styled-content style="fixed-case">H</jats:styled-content><jats:sub>1</jats:sub>–<jats:styled-content style="fixed-case">H</jats:styled-content><jats:sub>4</jats:sub>). The histamine<jats:styled-content style="fixed-case">H</jats:styled-content><jats:sub>4</jats:sub>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<jats:styled-content style="fixed-case">H</jats:styled-content><jats:sub>4</jats:sub>receptor ligands have rapidly increased our knowledge of<jats:styled-content style="fixed-case">H</jats:styled-content><jats:sub>4</jats:sub>receptor involvement in gastrointestinal processes both under physiological conditions and in models of disease. Strong evidence points towards a role for<jats:styled-content style="fixed-case">H</jats:styled-content><jats:sub>4</jats:sub>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<jats:styled-content style="fixed-case">H</jats:styled-content><jats:sub>4</jats:sub>receptors in gastrointestinal cancerogenesis, sensory signalling, and visceral pain as well as in gastric ulceration. These studies highlight the potential of<jats:styled-content style="fixed-case">H</jats:styled-content><jats:sub>4</jats:sub>receptor targeted therapy in the treatment of various gastrointestinal disorders such as inflammatory bowel disease, irritable bowel syndrome and cancer.</jats:p>