Involvement of TRPV4 in Serotonin-Evoked Scratching

Akiyama, Tasuku; Ivanov, M. A.; Nagamine, Masaki; Davoodi, Auva; Carstens, Mirela Iodi; Ikoma, Akihiko; Cevikbas, Ferda; Kempkes, Cordula; Buddenkotte, Joerg; Steinhoff, Martin; Carstens, Earl

doi:10.1038/jid.2015.388

Cited by 119 publications

(143 citation statements)

References 51 publications

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“…This alteration paralleled the time course of serotonin expression in the skin. We previously showed that TRPV4 appears to function as a downstream transducer of the serotonin-induced itch signal [5]. Increased gene expression levels of TRPV4 in DRG cells may be related to increased expression of serotonin.…”

Section: Discussionmentioning

confidence: 99%

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Mouse model of imiquimod-induced psoriatic itch

Sakai

Sanders

Youssef

et al. 2016

Pain

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Itch is a major indicator of psoriasis, but the underlying mechanisms behind this symptom are largely unknown. To investigate the neuronal mechanisms of psoriatic itch, we tested whether mice subjected to the imiquimod-induced psoriasis model exhibit itch-associated behaviors. Mice received daily topical applications of imiquimod to the rostral back skin for seven days. Imiquimod-treated mice exhibited a significant increase in spontaneous scratching behavior directed to the treated area as well as touch-evoked scratching (alloknesis). To characterize this model, we measured the mRNA expression levels of pruritogens and itch-relevant receptors/channels using real-time RT-PCR. The mRNA expression of MrgprA3, MrgprC11, and MrgprD decreased gradually over time in the dorsal root ganglion (DRG) cells. There was no significant change in the mRNA expression of TRPV1 or TRPA1 in DRG cells. TRPV4 mRNA expression was transiently increased in the DRG cells, while TRPM8 mRNA was significantly decreased. The mRNA expression levels of histidine decarboxylase and tryptophan hydroxylase 1, as well as the intensity of histamine and serotonin immunoreactivity, were transiently increased in the skin on day 2, returning to baseline by day 7. Histamine H1 receptor (H1R) antagonists, chlorpheniramine and olopatadine, significantly inhibited spontaneous scratching on day 2, but not day 7. Neither chlorpheniramine nor olopatadine affected alloknesis on day 2 or day 7. These results may reflect the limited antipruritic effects of H1R antagonists on human psoriasis. The imiquimod-induced psoriasis model appears to be useful for the investigation of itch and its sensitization in psoriasis.

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Section: Discussionmentioning

confidence: 99%

“…MrgprA3- and MrgprD-expressing neurons exhibited enhanced excitability in a mouse model of allergic contact dermatitis [29]. Additionally, thermosensitive TRP channels including TRPV1, TRPA1, TRPV4, and TRPM8 are activated downstreatm of GPCRs to mediate or modulate itch [5; 18; 35; 39]. …”

Section: Introductionmentioning

confidence: 99%

Mouse model of imiquimod-induced psoriatic itch

Sakai

Sanders

Youssef

et al. 2016

Pain

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“…showed that TRPV4 is not required for histamine-induced itch and, more markedly, that CQ-induced itch is increased in Trpv4 −/− mice (11). Exon 12, which encodes the pore loop and adjacent transmembrane domain, is deleted in the Trpv4 −/− mice that Akiyama et al used (36).…”

Section: Discussionmentioning

confidence: 99%

Facilitation of TRPV4 by TRPV1 is required for itch transmission in some sensory neuron populations

et al. 2016

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The transient receptor potential channels (TRPs) respond to chemical irritants and temperature. TRPV1 responds to the itch-inducing endogenous signal histamine, and TRPA1 responds to the itch-inducing chemical chloroquine. We showed that, in sensory neurons, TRPV4 is important for both chloroquine-and histamine-induced itch and that TRPV1 has a role in chloroquine-induced itch. Chloroquine-induced scratching was reduced in mice in which TRPV1 was knocked down or pharmacologically inhibited. Both TRPV4 and TRPV1 were present in some sensory neurons. Pharmacological blockade of either TRPV4 or TRPV1 significantly attenuated the Ca2+ response of sensory neurons exposed to histamine or chloroquine. Knockout of Trpv1 impaired Ca2+ responses and reduced scratching behavior evoked by a TRPV4 agonist, whereas knockout of Trpv4 did not alter TRPV1-mediated capsaicin responses. Electrophysiological analysis of human embryonic kidney (HEK) 293 cells coexpressing TRPV4 and TRPV1 revealed that the presence of both channels enhanced the activation kinetics of TRPV4 but not of TRPV1. Biochemical and biophysical studies suggested a close proximity between TRPV4 and TRPV1 in dorsal root ganglion neurons and in cultured cells. Thus, our studies identified TRPV4 as a channel that contributes to both histamine- and chloroquine-induced itch and indicated that the function of TRPV4 in itch signaling involves TRPV1-mediated facilitation. TRP facilitation through the formation of heteromeric complexes could be a prevalent mechanism by which the vast array of somatosensory information is encoded in sensory neurons.

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“…TRPV4 appears to play a role in itch perception in response to some, but not all pruritogens [143,144]. This is attributable at least in part to TRPV4 function in keratinocytes, where calcium influx through this channel triggers ERK phosphorylation.…”

Section: Contributions Of Trp Channels To Skin Biology and Pathophmentioning

confidence: 99%

TRP Channels in Skin Biology and Pathophysiology

Caterina¹,

Pang²

2016

Pharmaceuticals

137

126

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Ion channels of the Transient Receptor Potential (TRP) family mediate the influx of monovalent and/or divalent cations into cells in response to a host of chemical or physical stimuli. In the skin, TRP channels are expressed in many cell types, including keratinocytes, sensory neurons, melanocytes, and immune/inflammatory cells. Within these diverse cell types, TRP channels participate in physiological processes ranging from sensation to skin homeostasis. In addition, there is a growing body of evidence implicating abnormal TRP channel function, as a product of excessive or deficient channel activity, in pathological skin conditions such as chronic pain and itch, dermatitis, vitiligo, alopecia, wound healing, skin carcinogenesis, and skin barrier compromise. These diverse functions, coupled with the fact that many TRP channels possess pharmacologically accessible sites, make this family of proteins appealing therapeutic targets for skin disorders.

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Involvement of TRPV4 in Serotonin-Evoked Scratching

Cited by 119 publications

References 51 publications

Mouse model of imiquimod-induced psoriatic itch

Mouse model of imiquimod-induced psoriatic itch

Facilitation of TRPV4 by TRPV1 is required for itch transmission in some sensory neuron populations

TRP Channels in Skin Biology and Pathophysiology

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