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Sensory neuron-specific GPCR Mrgprs are itch receptors mediating chloroquine-induced pruritus.

Cell | Dec 24, 2009

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.

Pubmed ID: 20004959 RIS Download

Mesh terms: Animals | Capsaicin | Chloroquine | Ganglia, Spinal | Histamine | Humans | Mice | Pruritus | Receptors, G-Protein-Coupled | Sensory Receptor Cells

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Associated grants

  • Agency: NINDS NIH HHS, Id: R01 NS054791-01A1
  • Agency: NINDS NIH HHS, Id: NS054791
  • Agency: NINDS NIH HHS, Id: R01 NS054791-03
  • Agency: NINDS NIH HHS, Id: R01 NS054791
  • Agency: NHLBI NIH HHS, Id: HL038095
  • Agency: NEI NIH HHS, Id: T32 EY017203
  • Agency: NINDS NIH HHS, Id: P01 NS048499
  • Agency: NINDS NIH HHS, Id: NS048499
  • Agency: NINDS NIH HHS, Id: R01 NS054791-04
  • Agency: NINDS NIH HHS, Id: R01 NS054791-02
  • Agency: NIAMS NIH HHS, Id: R01 AR056318
  • Agency: Howard Hughes Medical Institute, Id: R01 HL038095
  • Agency: NHLBI NIH HHS, Id: DK074480
  • Agency: NIDDK NIH HHS, Id: R01 DK074480
  • Agency: NIDDK NIH HHS, Id: AR056318
  • Agency: NIAMS NIH HHS, Id:

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