Abstract
The histamine H4 receptor, belonging to the family of G-protein coupled receptors, is an increasingly attractive drug target. It plays an indispensable role in many cellular pathways, and numerous H4R ligands are being studied for the treatment of several inflammatory, allergic, and autoimmune disorders, including pulmonary fibrosis. Activation of H4R is involved in cytokine production and mediates mast cell activation and eosinophil chemotaxis. The importance of this receptor has also been shown in inflammatory models: peritonitis, respiratory tract inflammation, colitis, osteoarthritis, and rheumatoid arthritis. Recent studies suggest that H4R acts as a modulator in cancer, neuropathic pain, vestibular disorders, and type-2 diabetes, however, its role is still not fully understood.
Highlights
Histamine action via distinct receptors (H1 R–H4 R) modulates diverse physiological as well as pathological processes
Histamine receptors, numbered in the order of their discovery H1 R-H4 R, are G protein-coupled receptors (GPCRs) that constitute the largest family of cell surface receptors in humans and play a key role in cellular signaling
The discovery and pharmacological characterization of H4 R ligands especially antagonists, on mast cells, eosinophils, and T cells demonstrates the possibility of its involvement in inflammatory conditions/symptoms such as atopic dermatitis (AD), asthma, allergic rhinitis, rheumatoid arthritis (RA), and pruritus in humans
Summary
Histamine action via distinct receptors (H1 R–H4 R) modulates diverse physiological as well as pathological processes. Due to their differential receptor pharmacology and signal transduction properties, histamine has characteristic effects dependent upon the histamine receptor subtype it is bound to. The role of H4R in neuropathic pain transmission and other diseases is still controversial after nearly 20 years since its discovery. This may be due to biased signaling of histamine and H4 receptor agonists and differential effects on multiple signaling pathways in central and peripheral parts of the sensory nervous system. Gaining a deeper understanding of the interaction between Coronaviruses and the innate immune system of the host may shed light on the development and persistence of inflammation in the lungs and can possibly reduce the risk of lung inflammation caused by CoVs [5]
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