Common mechanism in endothelin-3 and PAF receptor function for anti-inflammatory responses.
Platelet-activating factor (PAF) is a potent lipid mediator that is implicated in numerous inflammatory diseases. Under inflammatory conditions, PAF is biosynthesized through the remodelling pathway and elicits many inflammatory responses through binding to its specific PAF receptor. Endogenous bioactive endothelins (ETs: ET-1, -2, and -3) are also considered potent inflammatory mediators that play a critical role in many inflammatory diseases. In this perspective, we provide a brief overview of possible common mechanisms in ETs and PAF receptor function for inflammatory responses. Accumulating evidence strongly suggests that ET-3, but not ET-1 and ET-2, can attenuate PAF-induced inflammation through direct binding of the Tyr-Lys-Asp (YKD) region in the peptide to PAF and its metabolite/precursor lyso-PAF, followed by inhibition of binding between PAF and its receptor. Additionally, YKD sequence-containing peptides may be useful as a novel type of anti-inflammatory drugs targeting this mechanism. These findings should lead to new treatment strategies for numerous inflammatory diseases by targeting the common mechanism in ET and PAF receptor function.
Faculty of Pharmacy, Iwaki Meisei University, 5-5-1, Chuodai-Iino, Iwaki, Fukushima 970-8551, Japan. Electronic address: a-sato@iwakimu.ac.jp.
Akira
A
Sato
Keiichi
K
Ebina
D000595:Amino Acid Sequence; D019334:Endothelin-3 / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D017466:Receptors, Endothelin / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*
D019334:Endothelin-3; D010455:Peptides; D010980:Platelet Membrane Glycoproteins; D017466:Receptors, Endothelin; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor
Anti-inflammatory drug; Endothelin-3; Inflammation; PAF receptor; Platelet-activating factor