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

Abstract

The functional role of histamine H 4 receptors (H 4 Rs) in the Gastrointestinal (GI) tract is reviewed, with particular reference to their involvement in the regulation of gastric mucosal defense and inflammation. H 4 Rs 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, H 4 R expression was reported to be altered in some pathological conditions, such as colitis and cancer. Functional studies have demonstrated protective effects of H 4 R 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.

Histamine Antagonists to Temper the Cytokine Overproduction in Gastrointestinal Cells Infected by SARS-CoV-2

“…E.g. it is possible to (1) suppress H4R in gastrointestinal cells with JNJ-7777120, to use (2) maraviroc to hamper infection via gp120 and use (3) Interestingly, Adami [M. Adami and G. Coruzzi (2014)] found that the H4R antagonist JNJ-7777120 is able to undo the gastric damage of indomethacin. The "ok" in the tox column of table-1 is based on their finding.…”

The Synthesis of 1,3,5‐triazine Derivatives and JNJ7777120 Analogues with Histamine H4 Receptor Affinity and Their Interaction with PTEN Promoter

“…Much of the drug research in H 4 R field is focused on the search for H 4 R antagonists because of possibilities for the treatment of different inflammatory conditions, e.g. skin diseases, airway diseases or bowel diseases . However, preclinical results show also utility of H 4 R ligands in cancer, neuropathic pain or vestibular disorder .…”

Suppression of Laser-Induced Choroidal Neovascularization by the Oral Medicine Targeting Histamine Receptor H4 in Mice

“…11,16 HRH4 is of particular importance for regulating immune cell functions, including chemotaxis and cytokine secretion, whereas HRH4 antagonists have shown anti-inflammatory, antihyperalgesic, and anti-allergic effects in several acute and chronic experimental rodent models. [17][18][19][20] We have previously reported that genetic depletion of Hrh4 and the anti-HRH4 chemicals in mice suppressed laser-induced CNV (laser-CNV). 21 Macrophages play a major role in ocular angiogenesis, including CNV in wet-AMD.…”