TRPA1 is required for histamine-independent, Mas-related G protein-coupled receptor-mediated itch
By Sarah R. Wilson, K. Gerhold, Amber Bifolck-Fisher, Qin Liu, Kush N. Patel, Xinzhong Dong, D. Bautista. Nature Neuroscience, 2011
599 citations recorded by the source corpus.
Itch, the unpleasant sensation that evokes a desire to scratch, accompanies numerous skin and nervous system disorders. In many cases, pathological itch is insensitive to antihistamine treatment. Recent studies have identified members of the Mas-related G protein–coupled receptor (Mrgpr) family that are activated by mast cell mediators and promote histamine-independent itch. MrgprA3 and MrgprC11 act as receptors for the pruritogens chloroquine and BAM8–22, respectively. However, the signaling pathways and transduction channels activated downstream of these pruritogens are largely unknown. We found that TRPA1 is the downstream target of both MrgprA3 and MrgprC11 in cultured sensory neurons and heterologous cells. TRPA1 is required for Mrgpr-mediated signaling, as sensory neurons from TRPA1-deficient mice exhibited markedly diminished responses to chloroquine and BAM8–22. Similarly, TRPA1-deficient mice displayed little to no scratching in response to these pruritogens. Our findings indicate that TRPA1 is an essential component of the signaling pathways that promote histamine-independent itch.
Subfields: Dermatology, Rheumatology, Sensory Systems
View Paper: https://www.semanticscholar.org/paper/63341a641fd494e8e7821691c4bda20d1e47df05
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Sensory Systems
Citations in the corpus
- TRP channels and pain. (2013, background): “Recent pharmacological studies further suggest that some GPCRs, such as the chloroquineactivated itch receptor MrgprA3, activate TRPA1 through a mechanism involving direct coupling to Gβγ subunits (Bautista et al. 2012, Wilson et al. 2011) (Figure 5b).”
- The Epithelial Cell-derived Atopic Dermatitis Cytokine TSLP Activates Neurons to Induce Itch (2013, unknown): “The itch compounds histamine, chloroquine (CQ), and BAM8-22 have been shown to activate 5%–20% of sensory neurons (Ikoma et al., 2006; Imamachi et al., 2009; Liu et al., 2009; Wilson et al., 2011) that express TRPA1 and/or TRPV1.”