[HTML][HTML] Sensory neuron-specific GPCR Mrgprs are itch receptors mediating chloroquine-induced pruritus

Q Liu, Z Tang, L Surdenikova, S Kim, KN Patel, A Kim… - Cell, 2009 - cell.com
Q Liu, Z Tang, L Surdenikova, S Kim, KN Patel, A Kim, F Ru, Y Guan, HJ Weng, Y Geng…
Cell, 2009cell.com
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 …
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 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.
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