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Pirt, a TRPV1 modulator, is required for histamine-dependent and -independent itch.

Patel KN, Liu Q, Meeker S, Undem BJ, Dong X - PLoS ONE (2011)

Bottom Line: Itch, or pruritus, is an important clinical problem whose molecular basis has yet to be understood.Here we show that Pirt, known to play a vital part in sensing pain through modulation of the transient receptor potential vanilloid 1 (TRPV1) channel, is also necessary for proper itch sensation.Our findings demonstrate that the function of Pirt extends beyond nociception via TRPV1 regulation to its role as a critical component in several itch signaling pathways.

View Article: PubMed Central - PubMed

Affiliation: The Solomon H. Snyder Department of Neuroscience, Center for Sensory Biology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.

ABSTRACT
Itch, or pruritus, is an important clinical problem whose molecular basis has yet to be understood. Recent work has begun to identify genes that contribute to detecting itch at the molecular level. Here we show that Pirt, known to play a vital part in sensing pain through modulation of the transient receptor potential vanilloid 1 (TRPV1) channel, is also necessary for proper itch sensation. Pirt(-/-) mice exhibit deficits in cellular and behavioral responses to various itch-inducing compounds, or pruritogens. Pirt contributes to both histaminergic and nonhistaminergic itch and, crucially, is involved in forms of itch that are both TRPV1-dependent and -independent. Our findings demonstrate that the function of Pirt extends beyond nociception via TRPV1 regulation to its role as a critical component in several itch signaling pathways.

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SLIGRL- and ET-1-induced responses are Pirt-dependent.(A) Cellular responses to SLIGRL (130 µM) are fewer in DRG neurons from Pirt−/− mice (n = 5 per genotype). (B) Pirt mutants (n = 11) scratch less than WT mice (n = 13) upon SLIGRL injection (0.1 µmol), but the difference is not statistically significant. (C, D) ET-1 (10 pmol) generates a decreased behavioral response in Pirt KO (n = 10) versus WT (n = 9). * p<0.05, ** p<0.001; two-tailed unpaired t-test.
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pone-0020559-g003: SLIGRL- and ET-1-induced responses are Pirt-dependent.(A) Cellular responses to SLIGRL (130 µM) are fewer in DRG neurons from Pirt−/− mice (n = 5 per genotype). (B) Pirt mutants (n = 11) scratch less than WT mice (n = 13) upon SLIGRL injection (0.1 µmol), but the difference is not statistically significant. (C, D) ET-1 (10 pmol) generates a decreased behavioral response in Pirt KO (n = 10) versus WT (n = 9). * p<0.05, ** p<0.001; two-tailed unpaired t-test.

Mentions: The peptide Ser-Leu-Ile-Gly-Arg-Leu-NH2 (SLIGRL), derived from the sequence of protease-activated receptor 2 (PAR2), which exhibits self-activation [25], produces a nonhistaminergic form of itch [26]. In vitro, we saw a marked reduction in the number of Pirt−/− DRG neurons responsive to SLIGRL (2.4% of WT neurons vs. 0.5% in KO, Fig. 3A). We observed a decrease in the number of scratching bouts upon SLIGRL injection (148 bouts in WT vs. 92 in KO, Fig. 3B), but this difference was not statistically significant (p = 0.16). This may be due to the more variable scratching response to SLIGRL in comparison to other pruritogens.


Pirt, a TRPV1 modulator, is required for histamine-dependent and -independent itch.

Patel KN, Liu Q, Meeker S, Undem BJ, Dong X - PLoS ONE (2011)

SLIGRL- and ET-1-induced responses are Pirt-dependent.(A) Cellular responses to SLIGRL (130 µM) are fewer in DRG neurons from Pirt−/− mice (n = 5 per genotype). (B) Pirt mutants (n = 11) scratch less than WT mice (n = 13) upon SLIGRL injection (0.1 µmol), but the difference is not statistically significant. (C, D) ET-1 (10 pmol) generates a decreased behavioral response in Pirt KO (n = 10) versus WT (n = 9). * p<0.05, ** p<0.001; two-tailed unpaired t-test.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3105090&req=5

pone-0020559-g003: SLIGRL- and ET-1-induced responses are Pirt-dependent.(A) Cellular responses to SLIGRL (130 µM) are fewer in DRG neurons from Pirt−/− mice (n = 5 per genotype). (B) Pirt mutants (n = 11) scratch less than WT mice (n = 13) upon SLIGRL injection (0.1 µmol), but the difference is not statistically significant. (C, D) ET-1 (10 pmol) generates a decreased behavioral response in Pirt KO (n = 10) versus WT (n = 9). * p<0.05, ** p<0.001; two-tailed unpaired t-test.
Mentions: The peptide Ser-Leu-Ile-Gly-Arg-Leu-NH2 (SLIGRL), derived from the sequence of protease-activated receptor 2 (PAR2), which exhibits self-activation [25], produces a nonhistaminergic form of itch [26]. In vitro, we saw a marked reduction in the number of Pirt−/− DRG neurons responsive to SLIGRL (2.4% of WT neurons vs. 0.5% in KO, Fig. 3A). We observed a decrease in the number of scratching bouts upon SLIGRL injection (148 bouts in WT vs. 92 in KO, Fig. 3B), but this difference was not statistically significant (p = 0.16). This may be due to the more variable scratching response to SLIGRL in comparison to other pruritogens.

Bottom Line: Itch, or pruritus, is an important clinical problem whose molecular basis has yet to be understood.Here we show that Pirt, known to play a vital part in sensing pain through modulation of the transient receptor potential vanilloid 1 (TRPV1) channel, is also necessary for proper itch sensation.Our findings demonstrate that the function of Pirt extends beyond nociception via TRPV1 regulation to its role as a critical component in several itch signaling pathways.

View Article: PubMed Central - PubMed

Affiliation: The Solomon H. Snyder Department of Neuroscience, Center for Sensory Biology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.

ABSTRACT
Itch, or pruritus, is an important clinical problem whose molecular basis has yet to be understood. Recent work has begun to identify genes that contribute to detecting itch at the molecular level. Here we show that Pirt, known to play a vital part in sensing pain through modulation of the transient receptor potential vanilloid 1 (TRPV1) channel, is also necessary for proper itch sensation. Pirt(-/-) mice exhibit deficits in cellular and behavioral responses to various itch-inducing compounds, or pruritogens. Pirt contributes to both histaminergic and nonhistaminergic itch and, crucially, is involved in forms of itch that are both TRPV1-dependent and -independent. Our findings demonstrate that the function of Pirt extends beyond nociception via TRPV1 regulation to its role as a critical component in several itch signaling pathways.

Show MeSH
Related in: MedlinePlus