Research ArticleSensory Perception

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

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Science Signaling  12 Jul 2011:
Vol. 4, Issue 181, pp. ra45
DOI: 10.1126/scisignal.2001925

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Itchy and Scratchy, But Not Painful

Although some types of itching can be relieved with antihistamines, most are not, such as the itching associated with the antimalarial chloroquine. The peptide SLIGRL is used to study histamine-independent itch and was thought to activate the PAR2 receptor. Liu et al. showed that this peptide instead activated MrgprC11, a member of the family of Mas-related G protein–coupled receptors. In addition, a shorter version of this peptide triggered increased sensitivity to thermal pain through PAR2, but did not elicit scratching. Thus, these findings suggest that MrgprC11 mediates histamine-independent itch, whereas PAR2 signaling evokes increased sensitivity to thermal pain, and clarify the identity of the receptors that should be therapeutically targeted for relief from these sensations.