Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0033774 (pruritus)
 14,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Protease-activated receptor 2(PAR2) is a member of protease-activated receptors(PARs). PAR2 distributed in tissues and cells(such as skin, airway epithelial cell, pancreas, etc.) has a broad biological effects, and is involved in pathogenesis of many diseases, such as mechanical pain, asthma, pain of pancreatic cancer, inflammation, pruritus, etc. Intervention of PAR2 will help us to identify the role of PAR2 in the mechanisms of diseases and in the development of new drugs. This article concentrates on the research progress of agonist, antagonist, and pepducin on PAR2.
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PMID:[Research progress in medicines on protease-activated receptor 2]. 2985 93

Protease-activated receptor 2 (PAR2) is a transmembrane receptor expressed by multiple tissues, including skin, with rapidly expanding knowledge regarding its roles. In the skin, PAR2 has extensively documented effects in promoting Th2 inflammation and pruritus; and its role in atopic dermatitis continues to be thoroughly studied. Numerous new investigations have shown a more complex range of activities potentially related to dermatologic diseases. Goal of this review is to outline emerging effects of PAR2 activation in the skin other than those related to immunologic and pruritic functions. Specifically, this work seeks to summarize current knowledge (and gaps) of PAR2 as a regulator of epidermal barrier, keratinocyte differentiation, cutaneous tumorigenesis and pigmentation. Additional focus will be placed on possible involvement in dermatologic disease and emergence as a therapeutic target.
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PMID:Update on protease-activated receptor 2 in cutaneous barrier, differentiation, tumorigenesis and pigmentation, and its role in related dermatologic diseases. 3097 31

Protease-activated receptor 2 (PAR2) has long been implicated in inflammatory and visceral pain, but the cellular basis of PAR2-evoked pain has not been delineated. Although PAR2-evoked pain has been attributed to sensory neuron expression, RNA-sequencing experiments show ambiguous F2rl1 mRNA detection. Moreover, many pharmacological tools for PAR2 are nonspecific, acting also on the Mas-related GPCR family (Mrg) that are highly enriched in sensory neurons. We sought to clarify the cellular basis of PAR2-evoked pain. We developed a PAR2-conditional knockout mouse and specifically deleted PAR2 in all sensory neurons using the PirtCre mouse line. Our behavioral findings show that PAR2 agonist-evoked mechanical hyperalgesia and facial grimacing, but not thermal hyperalgesia, are dependent on PAR2 expression in sensory neurons that project to the hind paw in male and female mice. F2rl1 mRNA is expressed in a discrete population (~4%) of mostly small-diameter sensory neurons that coexpress the Nppb and IL31ra genes. This cell population has been implicated in itch, but our work shows that PAR2 activation in these cells causes clear pain-related behaviors from the skin. Our findings show that a discrete population of DRG sensory neurons mediate PAR2-evoked pain.
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PMID:The cellular basis of protease-activated receptor 2-evoked mechanical and affective pain. 3235 32