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Sensory Neuron-Specific GPCR Mrgprs Are Itch Receptors Mediating Chloroquine-Induced Pruritus
Open accessAbstract
SUMMARY 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 anti-malarial 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 co-express Gastrin-Releasing Peptide, a peptide involved in itch sensation, and MrgprC11. Activation of these neurons with 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.
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Metadata
- Authors
- Liu, Q., Tang, Z., Surdenikova, L., Kim, S., Patel, K. N., Kim, A., Ru, F., Guan, Y., Weng, H.-J., Geng, Y., Undem, B. J., Kollarik, M., Chen, Z.-F., Anderson, D. J., & Dong, X.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2009-12
- Volume
- 139
- Issue
- 7
- Pages
- 1353-1365
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2157856809
- Cited by
- 813
- References
- 0
- FWCI
- 14.53
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Liu, Q., Tang, Z., Surdenikova, L., Kim, S., Patel, K. N., Kim, A., Ru, F., Guan, Y., Weng, H.-J., Geng, Y., Undem, B. J., Kollarik, M., Chen, Z.-F., Anderson, D. J., & Dong, X. (2009). Sensory Neuron-Specific GPCR Mrgprs Are Itch Receptors Mediating Chloroquine-Induced Pruritus. Cell. https://doi.org/10.1016/j.cell.2009.11.034
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