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Sensory neuron-specific GPCR Mrgprs are itch receptors mediating chloroquine-induced pruritus.
- Source :
-
Cell [Cell] 2009 Dec 24; Vol. 139 (7), pp. 1353-65. Date of Electronic Publication: 2009 Dec 10. - Publication Year :
- 2009
-
Abstract
- The cellular and molecular mechanisms mediating histamine-independent itch in primary sensory neurons are largely unknown. Itch induced by chloroquine (CQ) is a common side effect of this widely used antimalarial drug. Here, we show that Mrgprs, a family of G protein-coupled receptors expressed exclusively in peripheral sensory neurons, function as itch receptors. Mice lacking a cluster of Mrgpr genes display significant deficits in itch induced by CQ but not histamine. CQ directly excites sensory neurons in an Mrgpr-dependent manner. CQ specifically activates mouse MrgprA3 and human MrgprX1. Loss- and gain-of-function studies demonstrate that MrgprA3 is required for CQ responsiveness in mice. Furthermore, MrgprA3-expressing neurons respond to histamine and coexpress gastrin-releasing peptide, a peptide involved in itch sensation, and MrgprC11. Activation of these neurons with the MrgprC11-specific agonist BAM8-22 induces itch in wild-type but not mutant mice. Therefore, Mrgprs may provide molecular access to itch-selective neurons and constitute novel targets for itch therapeutics.<br /> (Copyright 2009 Elsevier Inc. All rights reserved.)
Details
- Language :
- English
- ISSN :
- 1097-4172
- Volume :
- 139
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Cell
- Publication Type :
- Academic Journal
- Accession number :
- 20004959
- Full Text :
- https://doi.org/10.1016/j.cell.2009.11.034