The Histamine H4 Receptor: A Novel Target for Safe Anti-inflammatory Drugs?

The functional role of histamine H4 receptors (H4Rs) in the Gastrointestinal (GI) tract is reviewed, with particular reference to their involvement in the regulation of gastric mucosal defense and inflammation. H4Rs have been detected in different cell types of the gut, including immune cells, paracrine cells, endocrine cells and neurons, from different animal species and humans; moreover, H4R expression was reported to be altered in some pathological conditions, such as colitis and cancer. Functional studies have demonstrated protective effects of H4R antagonists in several experimental models of gastric mucosal damage and intestinal inflammation, suggesting a potential therapeutic role of drugs targeting this new receptor subtype in GI disorders, such as allergic enteropathy, Inflammatory Bowel Disease (IBD), Irritable Bowel Syndrome (IBS) and cancer. kEywoRDs: Histamine H4 receptor; Stomach; Intestine. AbbREviAtions: CNS: Central Nervous System; GI: Gastrointestinal; H3Rs: H3 Receptors; H4Rs: H4 Receptors; IBD: Inflammatory Bowel Disease; IBS: Irritable Bowel Syndrome; IL-6: Interleukin-6; NSAIDs: Nonsteroidal Anti-inflammatory Drugs; TNBS: Trinitrobenzene Sulphonic Acid; TNF-α: Tumour Necrosis Factor-alpha; UC: Ulcerative Colitis.