Platelet activating factor (PAF)is a potent phospholipid mediator of inflammation. PAF acts on a single receptor (PAFR) that may be expressed on cellular and nuclear membranes of various cell types, especially leukocytes, platelets, endothelial cells, neuronal cells and microglia. PAF stimulates neutrophil chemotaxis and vascular permeability. PAF accumulates in the brain after cerebral.
An overview of PAF-R
Platelet activator factor receptor (PAF-R) is a phospholipid medium that has a variety of physiological functions and can respond to platelet activator (PAF). The PAF receptor results in a variety of biological responses, and is associated with intracellular signal transduction pathways, such as the conversion of phosphatidyl inositol, increased intracellular calcium concentration, and kinase activation and so on. For years, PAF-R has been a G protein coupled receptor representing therapeutic targets. Because PAF is the agonist of PAF-R, it will cause the process of mitogen-activated protein kinase (MAPK) pathway and lead to a proinflammatory cascade. PAF receptors exist in most of the major organs of the body, including the central nervous system (CNS), muscles and inflammatory cells.
Antagonists of PAF-R
PAF-R antagonists, a kind of naturally occurring agonist, these molecules can bind to PAF receptors and can competitively or noncompetitively displace PAF from binding sites on PAF-R. PAF-R antagonists can be used to reduce the incidence of bacterial infections and reduce deterioration. A great deal of structurally diverse molecules have been shown to act as antagonists to PAF-R. Many molecules can show antagonistic activity, and PAF-R antagonists can be broadly divided into four categories: (1) Structure-related synthetic PAF derivatives; (2) Synthetic compounds with no structural similarity to PAF; (3) Natural products; (4) Metal complexes. The thiazolium derivative CV-3988 is a amphoteric ion species with a similar structure to PAF，which was the first synthetic substance recognized as a PAF-R antagonist. In addition, WEB 2086 is also an effective PAF-R antagonist in humans, and significant side effects that may have prevented clinical trials have not been found.
PAF-R and diseases
PAF-R is a member of the G-protein-coupled receptor (GPCR) superfamily expressed on the surface of various cells and tissues. PAF-R is involved in a variety of pathophysiological activities, including respiratory and nervous system regulation, inflammation and immune response, as well as cardiovascular and reproductive activities. It is considered that PAF-R is a vital drug target for remedying inflammation, asthma, and cardiovascular disease.
Hyland, I. K., O'Toole, R. F., Smith, J. A., & Bissember, A. C. (2018). Progress in the Development of Platelet‐Activating Factor Receptor (PAFr) Antagonists and Applications in the Treatment of Inflammatory Diseases. ChemMedChem.