<scp>TRPV</scp>4 activates autonomic and behavioural warmth‐defence responses in <scp>W</scp>istar rats

Vizin, Robson Cristiano Lillo; Scarpellini, Carolina da Silveira; Ishikawa, Débora T.; Correa, Gabriela Monteiro; Souza, Cristiane Oliveira de; Gargaglioni, Luciane H.; Carrettiero, Daniel Carneiro; Bícego, Kênia C.; Almeida, Maria Camila

doi:10.1111/apha.12477

Cited by 39 publications

(47 citation statements)

References 54 publications

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“…Surely, they are no atavism because several functions of these receptors could be identified, for example regulation of barrier homoeostasis. Nevertheless, the broad function spectrum of these ectopic receptors is only marginally analysed to date . According to these results, also more ectopically expressed human ORs have been identified, and the functionality of ORs in non‐olfactory cell types has become better understood .…”

Section: Discussionmentioning

confidence: 99%

“…Remarkably, also a wide range of classic central nervous system (CNS) neuroreceptors, which are usually necessary for auditory and visual functions, could be found in the skin, such as opsin receptors and transient receptor potential channels. They seem to play an important role, for example, in permeability barrier homoeostasis, but their full function is also still under investigation …”

Section: Introductionmentioning

confidence: 99%

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Two olfactory receptors—OR2A4/7 andOR51B5—differentially affect epidermal proliferation and differentiation

Tsai

Veitinger

Peek

et al. 2016

Experimental Dermatology

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Olfactory receptors (ORs), which belong to the G-protein coupled receptor family, are expressed in various human tissues, including skin. Cells in non-olfactory tissues tend to express more than one individual OR gene, but function and interaction of two or more ORs in the same cell type has only been marginally analysed. Here, we revealed OR2A4/7 and OR51B5 as two new ORs in human skin cells and identified cyclohexyl salicylate and isononyl alcohol as agonists of these receptors. In cultured human keratinocytes, both odorants induce strong Ca signals that are mediated by OR2A4/7 and OR51B5, as demonstrated by the receptor knockdown experiments. Activation of corresponding receptors induces a cAMP-dependent pathway. Localization studies and functional characterization of both receptors revealed several differences. OR2A4/7 is expressed in suprabasal keratinocytes and basal melanocytes of the epidermis and influences cytokinesis, cell proliferation, phosphorylation of AKT and Chk-2 and secretion of IL-1. In contrast, OR51B5 is exclusively expressed in suprabasal keratinocytes, supports cell migration and regeneration of keratinocyte monolayers, influences Hsp27, AMPK1 and p38MAPK phosphorylation and interestingly, IL-6 secretion. These findings underline that different ORs perform diverse functions in cutaneous cells, and thus offering an approach for the modulated treatment of skin diseases and wound repair.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Two olfactory receptors—OR2A4/7 andOR51B5—differentially affect epidermal proliferation and differentiation

Tsai

Veitinger

Peek

et al. 2016

Experimental Dermatology

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“…To infer the putative consequences of woolly mammothspecific amino acid substitutions in thermoTRPs, we generated structural models of the ancestral Asian elephant/mammoth (AncGajah; Figure 1A) and ancestral mammoth (AncMammoth; Figure 1A) TRPA1, which mediates nocifensive (Karashima et al, 2009;Kwan et al, 2006;Vizin et al, 2015) and vascular responses to noxious cold (Aubdool et al, 2014) as well as generally potentiating responses to noxious stimuli (del Camino et al, 2010), and TRPV4, which mediates autonomic and behavioral responses to cold (Vizin et al, 2015). We found that the elephantid TRPA1 and TRPV4 proteins were predicted to adopt the common TRP channel structure, which is composed of a series of amino terminal ankyrin repeats (ARD), separated by a membrane proximal domain (MPD) from the six transmembrane helices (S1-S6) that form the ion-permeable pore in tetrameric channels ( Figure 4B).…”

Section: Substitutions In Temperature-sensitive Transient Receptor Pomentioning

confidence: 99%

Elephantid Genomes Reveal the Molecular Bases of Woolly Mammoth Adaptations to the Arctic

et al. 2015

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Woolly mammoths and living elephants are characterized by major phenotypic differences that have allowed them to live in very different environments. To identify the genetic changes that underlie the suite of woolly mammoth adaptations to extreme cold, we sequenced the nuclear genome from three Asian elephants and two woolly mammoths, and we identified and functionally annotated genetic changes unique to woolly mammoths. We found that genes with mammoth-specific amino acid changes are enriched in functions related to circadian biology, skin and hair development and physiology, lipid metabolism, adipose development and physiology, and temperature sensation. Finally, we resurrected and functionally tested the mammoth and ancestral elephant TRPV3 gene, which encodes a temperature-sensitive transient receptor potential (thermoTRP) channel involved in thermal sensation and hair growth, and we show that a single mammoth-specific amino acid substitution in an otherwise highly conserved region of the TRPV3 channel strongly affects its temperature sensitivity.

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“…The lack of such a direct confirmation is the major shortcoming of the Vizin et al . () study, as it leaves the door open for the possibility of an off‐target action, especially in view of the contradictory and largely negative results of the earlier studies discussed above (Liedtke & Friedman , Lee et al . , Huang et al .…”

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confidence: 90%

“…In the current issue of Acta Physiologica , Vizin et al . () report the results of a study aimed at establishing whether another TRP channel, vanilloid‐4 (V4), plays a similarly critical role in heat defences.…”

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confidence: 99%

The transient receptor potential vanilloid‐4 channel: detecting body temperatures that drive defences against mild warmth

Garami

Romanovsky

2015

Acta Physiologica

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Over the last two decades, many channels, including several of the transient receptor potential (TRP) channels, have been shown to be highly sensitive to temperature and proposed to serve as thermosensors for physiological functions and behaviours that depend on temperature. However, it is still largely unknown which TRP channels detect skin, brain and other body temperatures that drive physiological (autonomic) and behavioural cold and heat defences in mammals (Romanovsky 2014). Arguably, the only exception is the TRP channel melastatin-8 (M8), which has been shown to sense a decreased skin temperature to drive tail skin vasoconstriction, non-shivering thermogenesis and cold-avoidance (warmth-seeking) behaviour in rodents (Almeida et al. 2012). In the current issue of Acta Physiologica, Vizin et al. (2015) report the results of a study aimed at establishing whether another TRP channel, vanilloid-4 (V4), plays a similarly critical role in heat defences.TRPV4 is known to be activated by warmth (25-34°C) in vitro (Guler et al. 2002, Watanabe et al. 2002, but the earlier in vivo studies of its thermoregulatory role produced contradictory results. On one side, several groups showed that body temperature of TRPV4-knockout (Trpv4 À/À ) mice did not differ from that of wild-type littermates, whether under thermoneutral conditions or during cold or warmth exposure (Liedtke & Friedman 2003, Lee et al. 2005. These negative results seem to suggest that TRPV4 is not essential for thermoregulation. On the other hand, based on the increased withdrawal latencies in a tailimmersion test and on the increased preference for warmth observed in Trpv4 À/À mice, Lee et al. (2005) proposed that TRPV4 plays important roles in the avoidance responses caused by innocuous warmth (a thermoregulatory response) or noxious heat (a response to thermal pain). Yet, in a subsequent work, the same group argued against such a role for TRPV4 in either response (Huang et al. 2011).It should be noted, however, that thermophysiological studies in mice are notoriously tricky to conduct (Rudaya et al. 2005) and that any studies in knockout animals (typically mice) are often difficult to interpret due to the development of compensation for the knocked-out gene. To circumvent both the methodological and interpretational difficulties of studying genetically modified mice, pharmacological antagonists are often used in rat experiments. This is exactly the approach taken by Vizin et al. (2015).The authors showed that the intravenous administration of HC-067047, a potent TRPV4 antagonist (Everaerts et al. 2010), caused a rise in deep body temperature at an ambient temperature of 26°C (which was neutral in the experimental setup used) or 30°C (a low supraneutral temperature). No body temperature rise occurred at a subneutral ambient temperature of 22°C (at which TRPV4 channels in the skin were presumably not activated) or at a higher supraneutral ambient temperature of 32°C (at which multiple additional central and/or peripheral thermosensors can be speculated t...

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TRPV4 activates autonomic and behavioural warmth‐defence responses in Wistar rats

Abstract: Our results suggest, for the first time, that TRPV4 channel is involved in the recruitment of behavioural and autonomic warmth-defence responses to regulate core body temperature.

Cited by 39 publications

References 54 publications

Two olfactory receptors—OR2A4/7 andOR51B5—differentially affect epidermal proliferation and differentiation

Two olfactory receptors—OR2A4/7 andOR51B5—differentially affect epidermal proliferation and differentiation

Elephantid Genomes Reveal the Molecular Bases of Woolly Mammoth Adaptations to the Arctic

The transient receptor potential vanilloid‐4 channel: detecting body temperatures that drive defences against mild warmth

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