Functional Vanilloid Receptors in Cultured Normal Human Epidermal Keratinocytes

Inoué, Kaori; Koizumi, Schuichi; Fuziwara, Shigeyoshi; Denda, Sumiko; Inoue, Kazuhide; Denda, Mitsuhiro

doi:10.1006/bbrc.2002.6393

Cited by 252 publications

(215 citation statements)

References 27 publications

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“…The functional expression of TRPV1 has previously been demonstrated in human keratinocyte cell lines (20,21). However, a significant involvement of TRPV1 in the warmthevoked responses described in this study can most likely be excluded, given the following: 1) TRPV1 protein was not readily detectable in 308 cells; 2) capsaicin, a selective and efficacious TRPV1 agonist, failed to evoke a visible Ca 2ϩ response at doses that are saturating for neuronal or recombinant TRPV1; and 3) the heat activation threshold we observed in keratinocytes was ϳ9°C lower than that exhibited by TRPV1 in native (26,27) and recombinant (19) systems.…”

Section: Discussionmentioning

confidence: 95%

“…Mouse Keratinocytes Express Both TRPV3 and TRPV4 -Given the results described above and previous demonstrations of TRPV channel expression in keratinocytes in vivo (3,10,20,21), we explored whether any of the four known heat-sensitive TRPV subtypes were expressed in 308 cells. After isolation of poly(A) ϩ RNA, we performed reverse transcription-PCR using primers specific for mouse TRPV1-4 (Fig.…”

Section: Warm Temperatures Evoke a Rise In [Ca 2ϩ ] I In Mouse 308mentioning

confidence: 99%

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Warm Temperatures Activate TRPV4 in Mouse 308 Keratinocytes

Chung¹,

Lee²,

Caterina³

2003

Journal of Biological Chemistry

263

211

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Mammalian survival requires constant monitoring of environmental and body temperature. Recently, several members of the transient receptor potential vanilloid (TRPV) subfamily of ion channels have been identified that can be gated by increases in temperature into the warm (TRPV3 and TRPV4) or painfully hot (TRPV1 and TRPV2) range. In rodents, TRPV3 and TRPV4 proteins have not been detected in sensory neurons but are highly expressed in skin epidermal keratinocytes. Here, we show that in response to warm temperatures (>32°C), the mouse 308 keratinocyte cell line exhibits nonselective transmembrane cationic currents and Ca 2؉ influx. Both TRPV3 and TRPV4 are expressed in 308 cells. However, the warmth-evoked responses we observe most closely resemble those mediated by recombinant TRPV4 on the basis of their electrophysiological properties and sensitivity to osmolarity and the phorbol ester, 4␣-phorbol-12,13-didecanoate. Together, these data support the notion that keratinocytes are capable of detecting modest temperature elevations, strongly suggest that TRPV4 participates in these responses, and define a system for the cell biological analysis of warmth transduction.The perception of ambient temperature is a physiological process critical to the maintenance of body temperature and the avoidance of painful or dangerous thermal extremes. Since the identification of the heat-sensing ion channel TRPV1 (1), 1 which is activated by temperatures above 42°C, there has been a significant focus on potential thermosensory functions for this and other ion channels of the transient receptor potential family. TRPV2 (2) and TRPV3 (3-5) were first described as heat transducers operative at very hot (Ͼ52°C) and moderately warm (Ͼ34°C) temperatures, respectively. TRPV4, which was originally identified as an osmosensory ion channel (6 -9), can also be activated by warm temperatures (Ͼ34°C) (10, 11). In addition, two TRP proteins outside of the TRPV subfamily, TRPM8 (12, 13) and ANKTM1 (ankyrin repeat/transmembrane-containing ion channel) (14), have been identified as cold-activated ion channels expressed in sensory neurons.In mammals, the skin is extremely important for the transduction of thermal information and its transmission to the central nervous system. Cutaneous thermosensation has been largely attributed to the sensory nerves that innervate the dermal and epidermal layers of the skin. Recent reports, however, have suggested the possibility that other skin components, most notably keratinocytes, might also participate in temperature sensation. TRPV1 and TRPV2 are highly expressed in distinct subsets of sensory neurons (2). In humans, TRPV3 is also expressed in sensory neurons (5). In contrast, attempts to detect TRPV4 (9, 10) and TRPV3 (3) at the protein level in rodent sensory neurons have been unsuccessful. Rather, immunohistochemical studies of mouse and rat skin have revealed that keratinocytes exhibit the greatest degree of cutaneous TRPV3 (3) and TRPV4 (10) expression. In addition, although peripheral sensory neurons ...

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Section: Discussionmentioning

confidence: 95%

Section: Warm Temperatures Evoke a Rise In [Ca 2ϩ ] I In Mouse 308mentioning

confidence: 99%

Warm Temperatures Activate TRPV4 in Mouse 308 Keratinocytes

Chung¹,

Lee²,

Caterina³

2003

Journal of Biological Chemistry

263

211

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“…CPS triggers a VR1-dependent extracellular Ca 2 þ influx Stimulation of endogenous VR1 on different neuronal 27,35,36 and non neuronal cell types, 14,15,37 by CPS results in dosedependent influx of Ca 2 þ , which is inhibited by the VR1 antagonist, CPZ.…”

Section: Cps Triggers In a Dose-dependent Manner Distinct Pathways Ofmentioning

confidence: 99%

Distinct thymocyte subsets express the vanilloid receptor VR1 that mediates capsaicin-induced apoptotic cell death

et al. 2004

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Herein, we provide the first evidence on the capsaicin (CPS) receptor vanilloid receptor type-1 (VR1) by rat thymocytes, and its involvement in CPS-induced apoptosis. VR1 mRNA was identified by quantitative RT-PCR in CD5 þ thymocytes. By immunofluorescence and flow cytometry, we found that a substantial portion of CD5 þ thymocytes, namely CD4 þ and double negative (DN) cell subsets, express VR1 that was present on plasma membrane on discrete spots. By Western blot, VR1 protein was identified as a single band of 95 kDa. We also described that CPS could trigger two distinct pathways of thymocyte death, namely apoptosis and necrosis depending on the dose of CPS exposure. CPS-induced apoptosis involved intracellular free calcium (Ca 2 þ ) influx, phosphatidylserine exposure, mitochondrial permeability transmembrane pore (PTP) opening and mitochondrial transmembrane potential (DW m ) dissipation leading to cytochrome c release, activation of caspase-9 and -3 and oligonucleosomal DNA fragmentation. VR1 was functionally implicated in these events as they were completely abrogated by the VR1 antagonist, capsazepine (CPZ). Finally, we demonstrated that VR1 expression on distinct thymocytes was associated with the selective ability of CPS to trigger DNA fragmentation in VR1 þ CD4 þ and DN thymocytes. Overall, our results suggest that the expression of VR1 on thymocytes may function as a sensor of harmful stimuli present in the thymic environment.

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“…Numerous reports indicate that TRPV1 is widely expressed, beyond sensory afferents, on several non-neuronal cell-types of the skin, including epidermal and hair follicle keratinocytes, mast cells, dendritic (Langerhans) cells, sebocytes and endothelial cells [223][224][225][226][227][228][229][230][231][232][233][234][235][236]. Activation of nonneuronal TRPV1 channels significantly influences key functions of these cutaneous cells which may lead to the development of pruritus and pruritic disorders.…”

Section: The Role Of Trpv1 Expressed By Non-neuronal Cellsmentioning

confidence: 99%

TRP Channels and Pruritus

Tóth¹,

Bı́ró²

2013

TOPAINJ

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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.

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Functional Vanilloid Receptors in Cultured Normal Human Epidermal Keratinocytes

Cited by 252 publications

References 27 publications

Warm Temperatures Activate TRPV4 in Mouse 308 Keratinocytes

Warm Temperatures Activate TRPV4 in Mouse 308 Keratinocytes

Distinct thymocyte subsets express the vanilloid receptor VR1 that mediates capsaicin-induced apoptotic cell death

TRP Channels and Pruritus

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