Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Protease-activated receptor 2 (PAR2) is the second member of a new subfamily of G-protein coupled receptors: the protease-activated receptors (PARs). At present, four different PARs have been cloned and all of them share the same basic mechanism of activation. A serine protease cleaves the extended, extracellular N-terminus of the receptor at a specific site within the protein chain to expose an N-terminal tethered ligand domain, which binds to and activates the cleaved receptor. In this manner, trypsin and mast cell beta-tryptase activate PAR2. PARs are single use receptors because proteolytic activation is irreversible and the cleaved receptors are degraded in lysosomes. Thus, PARs play important roles in emergency situations, such as trauma and inflammation. Emerging evidence indicates that PAR2 is involved in the cardiovascular, pulmonary and gastrointestinal systems, where it controls inflammation and nociception. Work with selective agonists and knockout animals suggests a contribution of PAR2 to certain inflammatory diseases. Therefore, selective antagonists or agonists of these receptors may be useful therapeutic agents for the treatment of human diseases.
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PMID:Proteinase-activated receptor-2: physiological and pathophysiological roles. 1531 91

The following four possible pathways for itching sensation have been suggested by recent reports. 1) Histaminergic TRPV1-positive pathway: Although histamine-positive nerve fibers cannot strictly be classified as "itch specific" due to their excitation also by pure algogens (making them itch-selective), the existence of a subpopulation of nociceptors responsible for itching is strongly suggested. Moreover, the TRPV1-expressing neurons have been suggested to be the main sensors and mediators of itching. 2) Histaminergic TRPV1-negative pathway: The scratching behavior caused by itching was not different between capsaicin-pre-treated and vehicle-treated (control) mast cell-rich NC mice. This result suggests the existence of a capsaicin-insensitive (TRPV1-negative) histaminergic pathway. 3) Non-histaminergic PAR-2 pathway: Protease-activated receptor 2 (PAR-2) has been shown to play a role in the itching of atopic dermatitis (AD). The itch evoked by cowhage (a non-histaminergic pruritogen that activates PAR-2) is very similar in characteristics to the itch evoked by conditions such as AD. 4) Non-histaminergic serotonin (5-HT) pathway: 5-HT alone applied to the human skin evokes an itching sensation and has been suggested to be involved in the itching associated with pruritic diseases, such as polycythemia vera and cholestasis.
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PMID:Four Possible Itching Pathways Related to the TRPV1 Channel, Histamine, PAR-2 and Serotonin. 2404 91