Sensory neuron-specific GPCR Mrgprs are itch receptors mediating chloroquine-induced pruritus
| Autor: | Yun Guan, Marian Kollarik, Fei Ru, Xinzhong Dong, Hao Jui Weng, Seung Il Kim, Lenka Surdenikova, Zhou-Feng Chen, Yixun Geng, Zongxiang Tang, Andrew Kim, Kush N. Patel, Bradley J. Undem, Qin Liu, David J. Anderson |
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| Rok vydání: | 2008 |
| Předmět: |
Agonist
Sensory Receptor Cells medicine.drug_class HUMDISEASE Sensory system Biology General Biochemistry Genetics and Molecular Biology MOLNEURO Article Receptors G-Protein-Coupled chemistry.chemical_compound Mice Ganglia Spinal parasitic diseases medicine otorhinolaryngologic diseases Animals Humans Receptor skin and connective tissue diseases G protein-coupled receptor Biochemistry Genetics and Molecular Biology(all) Pruritus Chloroquine Sensory neuron eye diseases medicine.anatomical_structure chemistry Capsaicin Immunology Neuroscience Histamine |
| Zdroj: | Cell. 139(7) |
| ISSN: | 1097-4172 |
| Popis: | SummaryThe 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. |
| Databáze: | OpenAIRE |
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