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Sci. Signal., 12 July 2011
Vol. 4, Issue 181, p. ra45
[DOI: 10.1126/scisignal.2001925]


The Distinct Roles of Two GPCRs, MrgprC11 and PAR2, in Itch and Hyperalgesia

Qin Liu1*, Hao-Jui Weng1*, Kush N. Patel1*, Zongxiang Tang1,2, Haihua Bai1,3, Martin Steinhoff4,5, and Xinzhong Dong1,6{dagger}

1 Solomon H. Snyder Department of Neuroscience, Center for Sensory Biology, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.
2 Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing 210046, China.
3 Inner Mongolia University for the Nationalities, School of Life Science, 22 Huolinhe Street, Tongliao City 028043, China.
4 Department of Dermatology, University of California, San Francisco, CA 94143, USA.
5 Department of Surgery, University of California, San Francisco, CA 94143, USA.
6 Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

* These authors contributed equally to this work.

Abstract: Itch has been defined as an unpleasant skin sensation that triggers the urge to scratch. Primary sensory dorsal root ganglia neurons detect itch stimuli through peripheral axons in the skin, playing an important role in generating itch. Itch is broadly categorized as histaminergic (sensitive to antihistamines) or nonhistaminergic. The peptide Ser-Leu-Ile-Gly-Arg-Leu (SLIGRL) is an itch-inducing agent widely used to study histamine-independent itch. Here, we show that Mrgprs (Mas-related G protein–coupled receptors), particularly MrgprC11, rather than PAR2 (protease-activated receptor 2) as previously thought, mediate this type of itch. A shorter peptide, SLIGR, which specifically activates PAR2 but not MrgprC11, induced thermal pain hypersensitivity in mice but not a scratch response. Therefore, although both Mrgpr and PAR2 are SLIGRL-responsive G protein–coupled receptors present in dorsal root ganglia, each plays a specific role in mediating itch and pain.

{dagger} To whom correspondence should be addressed. E-mail: xdong2{at}

Citation: Q. Liu, H.-J. Weng, K. N. Patel, Z. Tang, H. Bai, M. Steinhoff, X. Dong, The Distinct Roles of Two GPCRs, MrgprC11 and PAR2, in Itch and Hyperalgesia. Sci. Signal. 4, ra45 (2011).

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