TRPA1 is required for histamine-independent, Mas-related G protein–coupled receptor–mediated itch

Wilson, Sarah; Gerhold, Kristin A.; Bifolck-Fisher, Amber; Liu, Qin; Patel, Krishna; Dong, Xinzhong; Bautista, Diana M.

doi:10.1038/nn.2789

Cited by 523 publications

(639 citation statements)

References 49 publications

Supporting

Mentioning

603

Contrasting

Unclassified

Order By: Relevance

“…1C), we tested whether TRPA1 mediates the UVR photocurrent. TRPA1 is activated by numerous noxious compounds, pungent chemicals, and GPCRs (27)(28)(29)(30)(31), and was recently implicated in an extraocular UVR phototransduction system mediating light avoidance responses in Drosophila larvae (32).…”

mentioning

confidence: 99%

UV light phototransduction activates transient receptor potential A1 ion channels in human melanocytes

Bellono

Kammel

Zimmerman

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

122

139

View full text Add to dashboard Cite

Human skin is constantly exposed to solar ultraviolet radiation (UVR), the most prevalent environmental carcinogen. Humans have the unique ability among mammals to respond to UVR by increasing their skin pigmentation, a protective process driven by melanin synthesis in epidermal melanocytes. The molecular mechanisms used by melanocytes to detect and respond to longwavelength UVR (UVA) are not well understood. We recently identified a UVA phototransduction pathway in melanocytes that is mediated by G protein-coupled receptors and leads to rapid calcium mobilization. Here we report that in human epidermal melanocytes physiological doses of UVR activate a retinal-dependent current mediated by transient receptor potential A1 (TRPA1) ion channels. The TRPA1 photocurrent is UVA-specific and requires G protein and phospholipase C signaling, thus contributing to UVAinduced calcium responses to mediate downstream cellular effects and providing evidence for TRPA1 function in mammalian phototransduction. Remarkably, TRPA1 activation is required for the UVR-induced and retinal-dependent early increase in cellular melanin. Our results show that TRPA1 is essential for a unique extraocular phototransduction pathway in human melanocytes that is activated by physiological doses of UVR and results in early melanin synthesis.

show abstract

mentioning

confidence: 99%

UV light phototransduction activates transient receptor potential A1 ion channels in human melanocytes

Bellono

Kammel

Zimmerman

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

122

139

View full text Add to dashboard Cite

show abstract

“…Apparently, TRPA1 plays a crucial role in the downstream signaling of both MrgprA3 and C11 [321,322]. Indeed, in TRPA1 KO mice, but not in TRPV1 KO and wildtype animals, the activation of neither MrgprA3 (by chloroquine) nor MrgprC11 (by BAM 8-22) resulted in itch related scratching behavior.…”

Section: Trpa1mentioning

confidence: 96%

“…Furthermore, in heterologous expression systems, activation of the Mrgprs was able to evoke Ca 2+ responses only in those cells in which they were coexpressed with TRPA1. Finally, pharmacological experiments suggested that MrgpcA3 was coupled to TRPA1 via the subunit of G proteins whereas MrgpcrC11 most probably signals via a PLC dependent pathway [321].…”

Section: Trpa1mentioning

confidence: 99%

TRP Channels and Pruritus

Tóth¹,

Bı́ró²

2013

TOPAINJ

View full text Add to dashboard Cite

Itch (pruritus) is one of the most often seen sensory phenomena in clinical practice. Recent neurophysiological findings proposed the existence of a novel pruriceptive system which includes a multitude of pruritogenic (itch-inducing) peripheral mediators, itch-selective pruriceptors, sensory afferent networks, spinal cord neurons, and certain central nervous system regions. In this review, we first introduce major features of the pruriceptive system. We then focus on defining the roles of transient receptor potential (TRP) ion channels in skin-coupled itch and provide compelling evidence that certain thermosensitive TRP channels (especially TRPV1, TRPV3, TRPV4, and TRPA1) are indeed key players in pruritus pathogenesis. Finally, we propose TRP-centered future experimental directions towards the therapeutic targeting of TRP channels in the clinical management of itch.

show abstract

“…Once introduced to human skin, both BAM8-22 and β-alanine induce severe non-histaminergic itch [31,32] . What is interesting is that both MrgprA3 and MrgprC11 trigger intracellular calcium signals and action potentials through TRPA1 and not TRPV1 activation [33] , indicating a distinct activation mechanism compared to histamine-induced itch signal transduction. MrgprA3 and MrgprC11 are mostly co-expressed in small diameter sensory neurons [31] .…”

Section: Peripheral Mechanisms Of Itch and Painmentioning

confidence: 98%

Molecular Mechanisms of Itch and Pain: An Overview

Lee

2015

Itch Pain

View full text Add to dashboard Cite

Itch and pain are two distinct sensory modalities elicited by noxious and pruritic stimuli, respectively. The cellular and electrophysiological characteristics of itch and pain are very similar; thus discerning the mechanical difference between these two sensory modalities has long been elusive. Recent advances in this field have revealed various neuronal receptors responsible for itch and pain signal transduction and transmission. These studies have identified a distinct sub-population of sensory neurons responsible for itch signal transduction. In addition, itch and pain information conveyed to the spinal cord are processed and regulated by distinct spinal cord neurons. Although both itch and pain senses are required for our daily lives, chronic and hyper-sensation of itch and pain results in a debilitating disease state. Studies have now begun to elucidate mechanisms for the sensitization of pain and itch and also to unravel counter-regulatory mechanisms between itch and pain at the spinal cord level. Interestingly, toll-like receptors (TLRs), an innate immune receptor, has been implicated in the central sensitization of both pain and itch. In this review, we will briefly provide an overview of the molecular mechanisms of itch and pain. Additionally, we will discuss the recently uncovered role of TLRs in itch and pain sensation.

show abstract

TRPA1 is required for histamine-independent, Mas-related G protein–coupled receptor–mediated itch

Cited by 523 publications

References 49 publications

UV light phototransduction activates transient receptor potential A1 ion channels in human melanocytes

UV light phototransduction activates transient receptor potential A1 ion channels in human melanocytes

TRP Channels and Pruritus

Molecular Mechanisms of Itch and Pain: An Overview

Contact Info

Product

Resources

About