Potent pruritogenic action of tryptase mediated by PAR-2 receptor and its involvement in anti-pruritic effect of nafamostat mesilate in mice

Ui, Haruna; Andoh, Tsugunobu; Lee, Jung‐Bum; Nishimura, Hiroshi; Kuraishi, Yasushi

doi:10.1016/j.ejphar.2005.11.021

Cited by 130 publications

(120 citation statements)

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“…20 At 10 mg/kg, the dose used in this study, FUT-175 inhibits scratching induced by tryptase but not by histamine or serotonin in mice. 48 Our results obtained with FUT-175 may be largely due to tryptase inhibition, because results obtained with an alternative human tryptase inhibitor, MPI-0442352, were similar, although less striking. The broad-spectrum inhibitor of both tryptic and nontryptic serine peptidases, SBTI, caused the most dramatic decrease in intestinal secretion, granulocyte infiltration, and histologic changes in response to TxA.…”

Section: Contributions Of Proteases To C Difficile Txa-induced Enteritismentioning

confidence: 59%

Protease-Activated Receptor 2, Dipeptidyl Peptidase I, and Proteases Mediate Clostridium difficile Toxin A Enteritis

et al. 2007

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Section: Contributions Of Proteases To C Difficile Txa-induced Enteritismentioning

confidence: 59%

Protease-Activated Receptor 2, Dipeptidyl Peptidase I, and Proteases Mediate Clostridium difficile Toxin A Enteritis

et al. 2007

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“…Tryptase, a PAR 2 agonist proteinase, induces scratching in mice, which is inhibited by anti-PAR 2 antibody and the PAR 2 antagonist FSLLRY-NH 2 (5). Scratching induced by compound 48/ 80, which degranulates mast cells, is mediated by histamine and tryptase (5). Different groups of primary sensory nerves may be involved in itch signals induced by histamine and tryptase (6).…”

mentioning

confidence: 99%

“…PAR 2 -activating peptide (PAR 2 -AP) provokes itch in the skin, especially atopic eczema, in humans (3) and it elicits scratching in mice (4). Tryptase, a PAR 2 agonist proteinase, induces scratching in mice, which is inhibited by anti-PAR 2 antibody and the PAR 2 antagonist FSLLRY-NH 2 (5). Scratching induced by compound 48/ 80, which degranulates mast cells, is mediated by histamine and tryptase (5).…”

mentioning

confidence: 99%

Activation of Proteinase-Activated Receptors Induces Itch-Associated Response Through Histamine-Dependent and -Independent Pathways in Mice

et al. 2008

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Abstract. Proteinase-activated receptor-2 (PAR 2 ) participates in itch, but the role of the other subtypes of this receptor remain unknown. To investigate this issue, scratching, an itch-related behavior, was observed following intradermal injections of the activating peptides of PAR 1-4 in mice. Activating peptides of PAR 1 , PAR 2 , and PAR 4 , but not PAR 3 , induced scratching. The antihistamine terfenadine suppressed scratching elicited by activating peptides of PAR 1 and PAR 4 , but not PAR 2 . These results suggest that PAR 1 , PAR 2 , and PAR 4 are involved in itch and that histamine is a cause of itch related to PAR 1 and PAR 4 , but not PAR 2 .

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“…This increases the vascular permeability and upregulates the expression of intercellular adhesion molecules (Steinhoff et al, 2000). Animal experiments have revealed that nafamostat mesylate, a synthetic protease inhibitor, can block tryptase-induced scratching behavior in mice (Ui et al, 2006). Nevertheless, most current studies are only in the in vitro stage of testing, and to date there has been no study on the relevant clinical applications.…”

Section: Discussionmentioning

confidence: 99%

Effect of the house dust mite allergen Der p 1 on tryptase release from human mast cells

Wang¹,

Yan²,

Xu³

et al. 2016

Genet. Mol. Res.

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ABSTRACT. This study aimed to investigate the effects of the house dust mite allergen Der p 1 on the secretion of tryptase from the human mast cell line HMC-1. Flow cytometry was used to determine the expression levels of protease-activated receptor-2 (PAR2) on the surface of HMC-1 cells. HMC-1 cells were treated with Der p 1, SLIGRL-NH 2 (PAR2 agonist), LRGILS-NH 2 (control peptide for PAR2), or Der p 1 + FSLLRY (PAR2 antagonist), and the tryptase levels were measured using enzyme-linked immunosorbent assay. The biological functions of PAR2 were determined using the calcium green indicator, and intracellular calcium fluorescence intensity in the different groups (Der p 1, SLIGRL-NH 2 , LRGILS-NH 2 , Der p 1 + FSLLRY, tryptase, tryptase + FSLLRY, or cell culture medium) was detected by laser scanning confocal microscopy. The mast cells expressed PAR2 receptor on their surfaces. Der p 1 alone induced a significant release of intracellular calcium and tryptase in HMC-1 cells compared with the SLIGRL-NH 2 treatment group and the control group. The combination of Der p 1 and FSLLRY partly inhibited intracellular calcium and tryptase release in HMC-1 cells compared with the Der p 1 treatment group. Moreover, tryptase induced a significant release of intracellular calcium

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Potent pruritogenic action of tryptase mediated by PAR-2 receptor and its involvement in anti-pruritic effect of nafamostat mesilate in mice

Cited by 130 publications

References 29 publications

Protease-Activated Receptor 2, Dipeptidyl Peptidase I, and Proteases Mediate Clostridium difficile Toxin A Enteritis

Protease-Activated Receptor 2, Dipeptidyl Peptidase I, and Proteases Mediate Clostridium difficile Toxin A Enteritis

Activation of Proteinase-Activated Receptors Induces Itch-Associated Response Through Histamine-Dependent and -Independent Pathways in Mice

Effect of the house dust mite allergen Der p 1 on tryptase release from human mast cells

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