Scratching behavior in mice induced by the proteinase-activated receptor-2 agonist, SLIGRL-NH2

Shimada, Steven G.; Shimada, Kelly A.; Collins, J. G.

doi:10.1016/j.ejphar.2005.11.012

Cited by 109 publications

(106 citation statements)

References 15 publications

Supporting

Mentioning

101

Contrasting

Order By: Relevance

“…For example, acute topical application of tacrolimus inhibits scratching induced by PAR 2 -activating peptide, but not histamine (29). In this context, scratching induced by SLIGRL-NH 2 , a PAR 2 -activating peptide, is not inhibited by an H 1 histamine-receptor antagonist (7,8), and distinct dorsal horn neurons may receive signals of cutaneous stimulation with PAR 2 -activating peptide and histamine (30). Taking these findings into account, the present results suggest that PAR 2 and tryptase are interesting target molecules for the development of novel drugs effective against anti-histamine-resistant pruritus, like that in atopic dermatitis.…”

Section: Discussionmentioning

confidence: 99%

“…Intradermal injection of PAR 2 -activating peptide elicits scratching in mice (7,8). Activating peptides of PAR 1 and PAR 4 , but not PAR 3 , also elicit scratching, but scratching induced by PAR 1 -and PAR 4 -activating, but not PAR 2 -activating, peptides is inhibited by an H 1 histamine-receptor antagonist, suggesting that PAR 1 -and PAR 4 -associated scratching involves histamine release from mast cells (8).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Involvement of Tryptase and Proteinase-Activated Receptor-2 in Spontaneous Itch-Associated Response in Mice With Atopy-like Dermatitis

Tsujii

Andoh

et al. 2009

J Pharmacol Sci

View full text Add to dashboard Cite

Abstract. This study investigated the involvement of tryptase and proteinase-activated receptor (PAR) subtypes in spontaneous scratching, an itch-associated behavior, in NC mice. This strain of mice showed chronic atopy-like dermatitis and severe spontaneous scratching, when kept a long time in a conventional environment. The trypsin-like serine proteinase inhibitor nafamostat mesilate (1 -10 mg/kg) dose-dependently inhibited spontaneous scratching in mice with dermatitis. The activity of tryptase was increased in the lesional skin, which was inhibited by nafamostat at a dose inhibiting spontaneous scratching. Enzyme histochemistry revealed the marked increase of toluidine blue-stained cells, probably mast cells, with tryptase activity in the dermis of the lesional skin. Intravenous injection of anti-PAR 2 antibody suppressed spontaneous scratching of mice with dermatitis. Intradermal injection of the PAR 2 -activating peptide SLI-GRL-NH 2 , but not PAR 1 , 3 , 4 -activating peptides, elicited scratching at doses of 10 -100 nmol/site in healthy mice. PAR 2 -immunoreactivity was observed in the epidermal keratinocytes in healthy and dermatitis mice. These results suggest that PAR 2 and serine proteinase(s), mainly tryptase, are involved in the itch of chronic dermatitis.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Involvement of Tryptase and Proteinase-Activated Receptor-2 in Spontaneous Itch-Associated Response in Mice With Atopy-like Dermatitis

Tsujii

Andoh

et al. 2009

J Pharmacol Sci

View full text Add to dashboard Cite

show abstract

“…In marked contrast, the identical application of cowhage spicules, as well as intradermal injection of PAR-2 and -4 agonists, elicited robust scratching in mice (Akiyama et al 2009c(Akiyama et al , 2010bShimada et al 2006;Tsujii et al 2009). Cowhage spicules contain mucunain, which acts via PAR-2 and PAR-4 to elicit itch in humans (Reddy et al 2008).…”

Section: Discussionmentioning

confidence: 99%

Facial injections of pruritogens or algogens elicit distinct behavior responses in rats and excite overlapping populations of primary sensory and trigeminal subnucleus caudalis neurons

Klein

Carstens

2011

Journal of Neurophysiology

View full text Add to dashboard Cite

Klein A, Carstens MI, Carstens E. Facial injections of pruritogens or algogens elicit distinct behavior responses in rats and excite overlapping populations of primary sensory and trigeminal subnucleus caudalis neurons. J Neurophysiol 106: 1078 -1088. First published June 8, 2011 doi:10.1152/jn.00302.2011In the present study, we investigated whether intradermal cheek injection of pruritogens or algogens differentially elicits hindlimb scratches or forelimb wipes in Sprague-Dawley rats, as recently reported in mice. We also investigated responses of primary sensory trigeminal ganglion (TG) and dorsal root ganglion (DRG) cells, as well as second-order neurons in trigeminal subnucleus caudalis (Vc), to pruritic and algesic stimuli. 5-HT was the most effective chemical to elicit dose-dependent bouts of hindlimb scratches directed to the cheek, with significantly less forelimb wiping, consistent with itch. Chloroquine also elicited significant scratching but not wiping. Allyl isothiocyanate (AITC; mustard oil) elicited dose-dependent wiping with no significant scratching. Capsaicin elicited equivalent numbers of scratch bouts and wipes, suggesting a mixed itch and pain sensation. By calcium imaging, ϳ6% of cultured TG and DRG cells responded to 5-HT. The majority of 5-HT-sensitive cells also responded to chloroquine, AITC, and/or capsaicin, and one-third responded to histamine. Using a chemical search strategy, we identified single units in Vc that responded to intradermal cheek injection of 5-HT. Most were wide dynamic range (WDR) or nociceptive specific (NS), and a few were mechanically insensitive. The large majority additionally responded to AITC and/or capsaicin and thus were not pruritogen selective. These results suggest that primary and second-order neurons responsive to pruritogens and algogens may utilize a population coding mechanism to distinguish between itch and pain, sensations that are behaviorally manifested by distinct hindlimb scratching and forelimb wiping responses.

show abstract

“…As mentioned above, some evidence suggests the involvement of PAR 2 in itch, but the involvement of the other PARs remains unknown. Thus, the present study was conducted to compare the itchinducing efficacy of selective agonists of PAR [1][2][3][4] and determine the involvement of histamine.…”

mentioning

confidence: 99%

“…Recently, proteinase-activated receptor 2 (PAR 2 ) has been shown to be involved in itch. 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).…”

mentioning

confidence: 99%

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

et al. 2008

View full text Add to dashboard Cite

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 .

show abstract

Scratching behavior in mice induced by the proteinase-activated receptor-2 agonist, SLIGRL-NH2

Cited by 109 publications

References 15 publications

Involvement of Tryptase and Proteinase-Activated Receptor-2 in Spontaneous Itch-Associated Response in Mice With Atopy-like Dermatitis

Involvement of Tryptase and Proteinase-Activated Receptor-2 in Spontaneous Itch-Associated Response in Mice With Atopy-like Dermatitis

Facial injections of pruritogens or algogens elicit distinct behavior responses in rats and excite overlapping populations of primary sensory and trigeminal subnucleus caudalis neurons

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

Contact Info

Product

Resources

About