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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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Related in: MedlinePlus

Nonhistaminergic itch requires Pirt.(A, B) CQ (200 µg) induces significantly less scratching behavior in Pirt−/− mice (n = 9) than WT controls (n = 8). (C) A smaller percentage of Pirt KO neurons respond to CQ (1 mM) compared to WT (n = 5 per genotype). (D, E) The 5HT2-selective agonist α-Me-5HT (30 µg) produces decreased scratching in KO mice (n = 8; WT, n = 13). (F) Responses to 5HT (10 µM) are unchanged in Pirt KO DRG neurons (n = 4 per genotype). * p<0.05, ** p<0.001, *** p<0.0001; two-tailed unpaired t-test.
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pone-0020559-g002: Nonhistaminergic itch requires Pirt.(A, B) CQ (200 µg) induces significantly less scratching behavior in Pirt−/− mice (n = 9) than WT controls (n = 8). (C) A smaller percentage of Pirt KO neurons respond to CQ (1 mM) compared to WT (n = 5 per genotype). (D, E) The 5HT2-selective agonist α-Me-5HT (30 µg) produces decreased scratching in KO mice (n = 8; WT, n = 13). (F) Responses to 5HT (10 µM) are unchanged in Pirt KO DRG neurons (n = 4 per genotype). * p<0.05, ** p<0.001, *** p<0.0001; two-tailed unpaired t-test.

Mentions: The antimalarial drug chloroquine (CQ) commonly produces itch as a side effect [15], [16] and this cannot be ameliorated by antihistamines [17], [18]. CQ also induces itch when injected into mice and is transduced in a histamine-independent manner by the G protein-coupled receptor (GPCR) MrgprA3 [19]. Pirt mutant mice show a severe reduction in the behavioral itch response to CQ (38 bouts in KO vs. 184 in WT, Fig. 2A, B). Accordingly, fewer DRG neurons from Pirt−/− mice (6.1%) respond to CQ compared to WT neurons (9.5%, Fig. 2C).


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)

Nonhistaminergic itch requires Pirt.(A, B) CQ (200 µg) induces significantly less scratching behavior in Pirt−/− mice (n = 9) than WT controls (n = 8). (C) A smaller percentage of Pirt KO neurons respond to CQ (1 mM) compared to WT (n = 5 per genotype). (D, E) The 5HT2-selective agonist α-Me-5HT (30 µg) produces decreased scratching in KO mice (n = 8; WT, n = 13). (F) Responses to 5HT (10 µM) are unchanged in Pirt KO DRG neurons (n = 4 per genotype). * p<0.05, ** p<0.001, *** p<0.0001; two-tailed unpaired t-test.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0020559-g002: Nonhistaminergic itch requires Pirt.(A, B) CQ (200 µg) induces significantly less scratching behavior in Pirt−/− mice (n = 9) than WT controls (n = 8). (C) A smaller percentage of Pirt KO neurons respond to CQ (1 mM) compared to WT (n = 5 per genotype). (D, E) The 5HT2-selective agonist α-Me-5HT (30 µg) produces decreased scratching in KO mice (n = 8; WT, n = 13). (F) Responses to 5HT (10 µM) are unchanged in Pirt KO DRG neurons (n = 4 per genotype). * p<0.05, ** p<0.001, *** p<0.0001; two-tailed unpaired t-test.
Mentions: The antimalarial drug chloroquine (CQ) commonly produces itch as a side effect [15], [16] and this cannot be ameliorated by antihistamines [17], [18]. CQ also induces itch when injected into mice and is transduced in a histamine-independent manner by the G protein-coupled receptor (GPCR) MrgprA3 [19]. Pirt mutant mice show a severe reduction in the behavioral itch response to CQ (38 bouts in KO vs. 184 in WT, Fig. 2A, B). Accordingly, fewer DRG neurons from Pirt−/− mice (6.1%) respond to CQ compared to WT neurons (9.5%, Fig. 2C).

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