scholarly journals FXYD6 promotes thermal nociception by regulating TRPV1

2021 ◽  
Vol 17 ◽  
pp. ???
Author(s):  
Hao Luo ◽  
Bing Cai ◽  
Jing Pan ◽  
Hai-Xiang Shi ◽  
Kai-Kai Wang ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Small Diameter ◽  
Receptor Potential ◽  
Transient Receptor Potential Channel ◽  
Hek293 Cells ◽  
Drg Neurons ◽  
Intraplantar Injection ◽  
Noxious Heat ◽  
Thermal Nociception ◽  
Transient Receptor

FXYD6, an unnecessary auxiliary subunit of Na+,K+-ATPase, is expressed in the nervous system. However, its functions remain largely unclear. In the present study, we find that FXYD6 is involved in the thermal nociception. FXYD6 was mainly expressed in small-diameter DRG neurons expressing transient receptor potential channel V1 (TRPV1). In the SNS-Cre/ Fxyd6F/F mice, loss of FXYD6 in these sensory neurons impaired the behavioral responses to noxious heat stimulus and intraplantar injection of capsaicin. The capsaicin-induced and TRPV1-mediated currents were decreased in the FXYD6–deficient DRG neurons. Heterologous expression of FXYD6 could increase the TRPV1 capsaicin-sensitive currents in HEK293 cells. Furthermore, we found that the negatively charged PGDEE motif in C-terminal of FXYD6 is required for the FXYD6/TRPV1 interaction and FXYD6-mediated enhancement of TRPV1. Disrupting the FXYD6/TRPV1 interaction with the TAT-PGDEE peptide could elevate the threshold of thermal nociception. Therefore, FXYD6 maintains the thermal nociception via interacting with TRPV1 channel in nociceptors.

Abstract 11605: Proteinase-Activated Receptor-2 is Responsible for Amplified Function of Transient Receptor Potential Channel A1 in Skeletal Muscle Sensory Neurons of Rats With Peripheral Artery Disease

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Jihong Xing ◽  
Jian Lu ◽  
Jianhua Li
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Peripheral Artery Disease ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Channel ◽  
Peripheral Artery ◽  
Drg Neurons ◽  
Artery Disease ◽  
Transient Receptor

Background: Limb ischemia occurs in peripheral artery disease (PAD). Sympathetic nerve activity that regulates blood flow directed to the limbs is augmented during exercise in this disease and transient receptor potential channel A1 (TRPA1) in thin-fiber muscle afferents contributes to the amplified sympathetic responses. The objective of this study was to determine the role played by proteinase-activated receptor-2 (PAR2) in regulating abnormal TRPA1 function. Methods: A rat model of femoral artery ligation was employed to study PAD. Dorsal root ganglion (DRG) tissues of control limbs and limbs with 24 hours of femoral occlusion were obtained to examine the protein levels of PAR2 using western blot analysis. Also, current responses induced by activation of TRPA1 in skeletal muscle DRG neurons of control limbs and ligated limbs were characterized using whole-cell patch clamp methods. All data are presented as mean ± SE. Results: Femoral occlusion significantly increased expression of PAR2 in DRG (optical density: 1.06±0.03 in control vs. 1.45±0.04 after occlusion, P< 0.05; n = 6 in each group). In addition, femoral occlusion amplified the amplitude of DRG current responses evoked by stimulation of TRPA1 with AITC (a TRPA1 agonist, 100 μM). The peak amplitude of TRPA1 currents was 0.28±0.03 nA in control and 0.41±0.04 nA ( P< 0.05 vs. control; n = 12 in each group) after occlusion, respectively. Activation of PAR2 with SL-NH2 (a PAR2 agonist, 100 μM) increased the TRPA1 currents by 78±10% in DRG neurons of control limb and by 125±10% in DRG neurons of ligated limb ( P< 0.05 vs. control; n = 8 in each group). Moreover, the potentiating effects of PAR2 activation were significantly inhibited by application of phospholipase C (PLC) inhibitors or phosphatidylinositol-4,5-bisphosphate (PIP2). Conclusions: A functional interaction in PAR2 and TRPA1 in muscle sensory nerves likely contributes to the amplified sympathetic responsiveness observed in PAD and that the PLC/PIP2 is engaged in sensitization mechanism of TRPA1. These findings provide a pathophysiological basis for autonomic responses during exercise activity in this disease, which may further help to aim at a potential therapeutic approach for improvement of blood flow in PAD patients.

scholarly journals A tingling sanshool derivative excites primary sensory neurons and elicits nocifensive behavior in rats

2011 ◽  
Vol 105 (4) ◽  
pp. 1701-1710 ◽  
Author(s):  
Amanda H. Klein ◽  
Carolyn M. Sawyer ◽  
Karen L. Zanotto ◽  
Margaret A. Ivanov ◽  
Susan Cheung ◽  
...  
Keyword(s):  
Dorsal Root ◽  
Transient Receptor Potential ◽  
Thermal Sensitivity ◽  
Receptor Potential ◽  
Size Distributions ◽  
Mechanical Sensitivity ◽  
Drg Neurons ◽  
Intraplantar Injection ◽  
Cinnamic Aldehyde ◽  
Transient Receptor

Szechuan peppers contain hydroxy-α-sanshool that imparts desirable tingling, cooling, and numbing sensations. Hydroxy-α-sanshool activates a subset of sensory dorsal root ganglion (DRG) neurons by inhibiting two-pore potassium channels. We presently investigated if a tingle-evoking sanshool analog, isobutylalkenyl amide (IBA), excites rat DRG neurons and, if so, if these neurons are also activated by agonists of TRPM8, TRPA1, and/or TRPV1. Thirty-four percent of DRG neurons tested responded to IBA, with 29% of them also responding to menthol, 29% to cinnamic aldehyde, 66% to capsaicin, and subsets responding to two or more transient receptor potential (TRP) agonists. IBA-responsive cells had similar size distributions regardless of whether they responded to capsaicin or not; cells only responsive to IBA were larger. Responses to repeated application of IBA at a 5-min interstimulus interval exhibited self-desensitization (tachyphylaxis). Capsaicin did not cross-desensitize responses to IBA to any greater extent than the tachyphylaxis observed with repeated IBA applications. These findings are consistent with psychophysical observations that IBA elicits tingle sensation accompanied by pungency and cooling, with self-desensitization but little cross-desensitization by capsaicin. Intraplantar injection of IBA elicited nocifensive responses (paw licking, shaking-flinching, and guarding) in a dose-related manner similar to the effects of intraplantar capsaicin and serotonin. IBA had no effect on thermal sensitivity but enhanced mechanical sensitivity at the highest dose tested. These observations suggest that IBA elicits an unfamiliar aversive sensation that is expressed behaviorally by the limited response repertoire available to the animal.

scholarly journals Capsaicin and its analogues impede nocifensive response of Caenorhabditis elegans to noxious heat

2020 ◽  
Author(s):  
Bruno Nkambeu ◽  
Jennifer Ben Salem ◽  
Francis Beaudry
Keyword(s):  
Transient Receptor Potential ◽  
Curcuma Longa ◽  
Receptor Potential ◽  
Zingiber Officinale ◽  
Transient Receptor Potential Channel ◽  
Plant Metabolites ◽  
Noxious Heat ◽  
Secondary Plant Metabolites ◽  
C Elegans ◽  
Transient Receptor

AbstractCapsaicin is the most abundant pungent molecule identified in red chili peppers, and it is widely used for food flavoring, in pepper spray for self-defense devices and recently in ointments for the relief of neuropathic pain. Capsaicin and several other related vanilloid compounds are secondary plant metabolites. Capsaicin is a selective agonist of the transient receptor potential channel, vanilloid subfamily member 1 (TRPV1). After exposition to vanilloid solution, C. elegans wild type (N2) and mutants were placed on petri dishes divided in quadrants for heat stimulation. Thermal avoidance index was used to phenotype each tested C. elegans experimental groups. The data revealed for the first-time that capsaicin can impede nocifensive response of C. elegans to noxious heat (32°C – 35°C) following a sustained exposition. The effect was reversed 6h post capsaicin exposition. Additionally, we identified the capsaicin target, the C. elegans transient receptor potential channel OCR-2. Further experiments also undoubtedly revealed anti-nociceptive effect for capsaicin analogues, including ginger (Zingiber officinale) and turmeric (Curcuma longa) secondary metabolites.

scholarly journals Teriparatide improves pain-related behavior and prevents bone loss in ovariectomized mice

2019 ◽  
Vol 28 (1) ◽  
pp. 230949901989319 ◽  
Author(s):  
Sho Kato ◽  
Hiroki Wakabayashi ◽  
Taro Nakagawa ◽  
Gaku Miyamura ◽  
Yohei Naito ◽  
...  
Keyword(s):  
Bone Loss ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Channel ◽  
Inhibitory Effect ◽  
Mechanical Hyperalgesia ◽  
Drg Neurons ◽  
Ovariectomized Mice ◽  
Hind Limbs ◽  
Transient Receptor

Purpose: The aim of this study was to examine the inhibitory effect of teriparatide (TPTD) on pain and on bone loss in ovariectomized (OVX) mice. The mechanism of osteoporotic pain in OVX mice was evaluated through an examination of pain-related behavior as well as immunohistochemical examinations. Methods: Eight-week-old female ddY mice were OVX and assigned to one of three groups: (1) OVX mice treated with vehicle (OVX), (2) OVX mice treated with teriparatide (OVX-TPTD), or (3) SHAM-operated mice treated with vehicle (SHAM). Starting immediately after surgery, vehicle or TPTD was injected subcutaneously. After a 4-week treatment, mechanical sensitivity was tested using von Frey filaments. The proximal tibial metaphyses were analyzed three-dimensionally by microcomputed tomography (μCT). Calcitonin gene-related peptide (CGRP) and transient receptor potential channel vanilloid 1 (TRPV1) expressions in L3–5 dorsal root ganglion (DRG) neurons were examined using immunohistochemistry. Results: Ovariectomy induced bone loss and mechanical hyperalgesia in the hind limbs with upregulation of CGRP and TRPV1 expressions in DRG neurons innervating the hind limbs. Bone loss was prevented more effectively in the OVX-TPTD mice than in the OVX mice. Furthermore, mechanical hyperalgesia and upregulation of CGRP and TRPV1 expressions were significantly lower in the OVX-TPTD mice than in the OVX mice. Conclusion: TPTD treatment prevented ovariectomy-induced bone loss and ovariectomy-induced mechanical hyperalgesia in hind limbs, and it suppressed CGRP and TRPV1 expressions in DRG neurons. These results suggest that TPTD is useful for the treatment of osteoporotic pain in postmenopausal women.

scholarly journals Resiniferatoxin hampers the nocifensive response of Caenorhabditis elegans to noxious heat, and pathway analysis revealed that the Wnt signaling pathway is involved

2021 ◽  
Author(s):  
Jennifer Ben Salem ◽  
Bruno Nkambeu ◽  
Dina Arvanitis ◽  
Francis Beaudry
Keyword(s):  
Caenorhabditis Elegans ◽  
Wnt Signaling ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Channel ◽  
Pathway Enrichment Analysis ◽  
Vanilloid Receptors ◽  
Noxious Heat ◽  
C Elegans ◽  
Transient Receptor

Resiniferatoxin (RTX) is a metabolite extracted from Euphorbia resinifera. RTX is a potent capsaicin analog with specific biological activities resulting from its agonist activity with the transient receptor potential channel vanilloid subfamily member 1 (TRPV1). RTX has been examined as a pain reliever, and more recently, investigated for its ability to desensitize cardiac sensory fibers expressing TRPV1 to improve chronic heart failure (CHF) outcomes using validated animal models. Caenorhabditis elegans (C. elegans) expresses orthologs of vanilloid receptors activated by capsaicin, producing antinociceptive effects. Thus, we used C. elegans to characterize the antinociceptive properties and performed proteomic profiling to uncover specific signaling networks. After exposure to RTX, wild-type (N2) and mutant C. elegans were placed on petri dishes divided into quadrants for heat stimulation. The thermal avoidance index was used to phenotype each tested C. elegans experimental group. The data revealed for the first time that RTX can hamper the nocifensive response of C. elegans to noxious heat. The effect was reversed 6 h after RTX exposure. Additionally, we identified the RTX target, the C. elegans transient receptor potential channel OCR-3. The proteomics and pathway enrichment analysis results suggest that Wnt signaling is triggered by the agonistic effects of RTX on C. elegans vanilloid receptors.

scholarly journals Function of the Porcine TRPC1 Gene in Myogenesis and Muscle Growth

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 147
Author(s):  
Yu Fu ◽  
Peng Shang ◽  
Bo Zhang ◽  
Xiaolong Tian ◽  
Ruixue Nie ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Growth Traits ◽  
Expression Profiles ◽  
Muscle Growth ◽  
Receptor Potential ◽  
Transient Receptor Potential Channel ◽  
Nucleotide Polymorphisms ◽  
Pig Breeds ◽  
Muscle Tissues ◽  
Transient Receptor

In animals, muscle growth is a quantitative trait controlled by multiple genes. Previously, we showed that the transient receptor potential channel 1 (TRPC1) gene was differentially expressed in muscle tissues between pig breeds with divergent growth traits base on RNA-seq. Here, we characterized TRPC1 expression profiles in different tissues and pig breeds and showed that TRPC1 was highly expressed in the muscle. We found two single nucleotide polymorphisms (SNPs) (C-1763T and C-1604T) in TRPC1 that could affect the promoter region activity and regulate pig growth rate. Functionally, we used RNAi and overexpression to illustrate that TRPC1 promotes myoblast proliferation, migration, differentiation, fusion, and muscle hypertrophy while inhibiting muscle degradation. These processes may be mediated by the activation of Wnt signaling pathways. Altogether, our results revealed that TRPC1 might promote muscle growth and development and plays a key role in Wnt-mediated myogenesis.

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