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Abstract
The detection of pruritic (itchy) stimuli is mediated by a variety of receptors and channels expressed by primary sensory neurons. The G protein-coupled receptor (GPCR) MRGPRD is selectively expressed by a subset of mouse non-peptidergic nociceptors and functions as the molecular receptor for the itch-inducing chemical β-alanine. However, the channels responsible for generating electrical signals downstream of MRGPRD remain unclear. Here, we found that a member of the canonical TRP channel family, TRPC3, is highly expressed in MRGPRD+ non-peptidergic nociceptors, raising the possibility of whether TRPC3 functions as a downstream channel in the MRGPRD signaling pathway. We tested TrpC3 null mice for β-alanine induced itch, and found that these mice exhibit normal responses to β-alanine. At the cellular level, calcium influx triggered by β-alanine is also unchanged in cultured DRG neurons from TrpC3 null mice compared to wild type. Together, our results demonstrate that mouse TrpC3 is dispensable for β-alanine-induced acute itch.
Highlights
The detection of pruritic stimuli is mediated by a variety of receptors and channels expressed by primary sensory neurons
TRPC3 has been shown to be required for the cellular response to IgG immune complex (IgG-IC), a pain-inducing inflammatory compound that binds to the G protein-coupled receptor (GPCR) FcγRI, which in turn is coupled to TRPC3 through the Syk-PLC-IP3 pathway[14]
We found that TrpC3 is expressed at high levels in both thoracic and lumbar level dorsal root ganglia (DRG) at the beginning of adulthood (P21), but its expression is barely detectable at P0, suggesting that expression of TrpC3 steadily increases during postnatal development (Fig. 1A–H)
Summary
The detection of pruritic (itchy) stimuli is mediated by a variety of receptors and channels expressed by primary sensory neurons. The G protein-coupled receptor (GPCR) MRGPRD is selectively expressed by a subset of mouse non-peptidergic nociceptors and functions as the molecular receptor for the itch-inducing chemical β-alanine. Transient receptor potential (TRP) channels comprise a superfamily of more than 30 membrane-bound proteins that form nonselective cation channels when assembled into homo- or hetero-tetramers These TRP channels detect temperature, pH, osmolality, mechanical stimuli, and various endogenous and exogenous ligands, and play prominent functional roles in sensory signaling in mammals[4,5]. A number of these channels, including TRPA1, TRPM8, and TRPV1, are highly expressed by primary sensory neurons and mediate thermal, cold, pain, and chemical sensations[6,7,8]. Given the high degree of co-expression we found between TRPC3 and MRGPRD, we hypothesized that TRPC3 functions as a downstream transduction channel of MRGPRD to provide depolarizing signal, or to amplify signals
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