Abstract
Proteases, like thrombin, trypsin, cathepsins, or tryptase, can signal to cells by cleaving in a specific manner, a family of G protein-coupled receptors, the protease-activated receptors (PARs). Proteases cleave the extracellular N-terminal domain of PARs to reveal tethered ligand domains that bind to and activate the receptors. Recent evidence has supported the involvement of PARs in inflammation and pain. Activation of PAR1, PAR2, and PAR4 either by proteinases or by selective agonists causes inflammation inducing most of the cardinal signs of inflammation: swelling, redness, and pain. Recent studies suggest a crucial role for the different PARs in innate immune response. The role of PARs in the activation of pain pathways appears to be dual. Subinflammatory doses of PAR2 agonists induce hyperalgesia and allodynia, and PAR2 activation has been implicated in the generation of inflammatory hyperalgesia. In contrast, subinflammatory doses of PAR1 or PAR4 increase nociceptive threshold, inhibiting inflammatory hyperalgesia, thereby acting as analgesic mediators. PARs have to be considered as an additional subclass of G protein-coupled receptors that are active participants to inflammation and pain responses and that could constitute potential novel therapeutic targets.
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Abbreviations | ||
ACE | = | angiotensin converting enzyme |
TNF-α | = | tumor necrosis alpha |
PAR | = | protease activated receptor |
PAR-APs | = | PAR activating peptides |
DRG | = | dorsal root ganglia |
SP | = | substance P |
CGRP | = | calcitonin gene-related peptide. |
Abbreviations | ||
ACE | = | angiotensin converting enzyme |
TNF-α | = | tumor necrosis alpha |
PAR | = | protease activated receptor |
PAR-APs | = | PAR activating peptides |
DRG | = | dorsal root ganglia |
SP | = | substance P |
CGRP | = | calcitonin gene-related peptide. |