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

Liu Q, Tang ZX, Surdenikova L, Kim SI, Patel KN, Kim A, Ru F, Guan Y, Weng H-J, Geng YX, Undem BJ, Kollarik M, Chen ZF, Anderson DJ, Dong XZ (2009). Cell, 139(7):1353-1365. PMID:20004959 Read More

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.

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Posted on October 6, 2009
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