Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Sci. Signal., 12 July 2011
Vol. 4, Issue 181, p. ra45
[DOI: 10.1126/scisignal.2001925]
RESEARCH ARTICLES
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
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.
To whom correspondence should be addressed. E-mail: xdong2{at}jhmi.edu
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).
Potentiation of the Transient Receptor Potential Vanilloid 1 Channel Contributes to Pruritogenesis in a Rat Model of Liver Disease.
M. Belghiti, J. Estevez-Herrera, C. Gimenez-Garzo, A. Gonzalez-Usano, C. Montoliu, A. Ferrer-Montiel, V. Felipo, and R. Planells-Cases (2013)
J. Biol. Chem.
288, 9675-9685
|Abstract »|Full Text »|PDF »
Inhibitory Influence of the Hexapeptidic Sequence SLIGRL on Influenza A Virus Infection in Mice.
R. J. Betts, T. S. Mann, and P. J. Henry (2012)
J. Pharmacol. Exp. Ther.
343, 725-735
|Abstract »|Full Text »|PDF »
Mechanisms of Itch Evoked by {beta}-Alanine.
Q. Liu, P. Sikand, C. Ma, Z. Tang, L. Han, Z. Li, S. Sun, R. H. LaMotte, and X. Dong (2012)
J. Neurosci.
32, 14532-14537
|Abstract »|Full Text »|PDF »
Pruriceptive spinothalamic tract neurons: physiological properties and projection targets in the primate.
S. Davidson, X. Zhang, S. G. Khasabov, H. R. Moser, C. N. Honda, D. A. Simone, and G. J. Giesler Jr. (2012)
J Neurophysiol
108, 1711-1723
|Abstract »|Full Text »|PDF »
In vivo responses of cutaneous C-mechanosensitive neurons in mouse to punctate chemical stimuli that elicit itch and nociceptive sensations in humans.
C. Ma, H. Nie, Q. Gu, P. Sikand, and R. H. LaMotte (2012)
J Neurophysiol
107, 357-363
|Abstract »|Full Text »|PDF »
Intracellular Signaling and the Origins of the Sensations of Itch and Pain.
