scholarly journals Vanilloids Hamper Caenorhabditis elegans Response to Noxious Heat

2020 ◽  
Author(s):  
Bruno Nkambeu ◽  
Jennifer Ben Salem ◽  
Francis Beaudry
Keyword(s):  
Caenorhabditis Elegans ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Quantitative Structure ◽  
Structure Property ◽  
Neuroprotective Effects ◽  
Noxious Heat ◽  
C Elegans ◽  
Quantitative Structure Property Relationships

AbstractEugenol, a known vanilloid, was frequently used in dentistry as a local analgesic in addition, antibacterial and neuroprotective effects were also reported. Eugenol, capsaicin and many vanilloids are interacting with the transient receptor potential vanilloid 1 (TRPV1) in mammals and are activated by noxious heat. The pharmacological manipulation of the TRPV1 has been shown to have therapeutic value. Caenorhabditis elegans (C. elegans) express TRPV orthologs (e.g. OCR-2, OSM-9) and it is a commonly used animal model system to study nociception as it displays a well-defined and reproducible nocifensive behavior. After exposure to vanilloid solutions, 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 results showed that eugenol, vanillin and zingerone can hamper nocifensive response of C. elegans to noxious heat (32°C – 35°C) following a sustained exposition. Also, the effect was reversed 6h post exposition. Furthermore, eugenol and vanillin did not target specifically the OCR-2 or OSM-9 but zingerone did specifically target the OCR-2 similarly to capsaicin. Further structural and physicochemical analyses were performed. Key parameters for quantitative structure-property relationships (QSPR), quantitative structure-activity relationships (QSAR) and frontier orbital analyses suggest similarities and dissimilarities amongst the tested vanilloids and capsaicin in accordance with the relative anti-nociceptive effects observed.

scholarly journals OSM-9 and OCR-2 TRPV channels are accessorial warm receptors in Caenorhabditis elegans temperature acclimatisation

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Kohei Ohnishi ◽  
Shigeru Saito ◽  
Toru Miura ◽  
Akane Ohta ◽  
Makoto Tominaga ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Transient Receptor Potential ◽  
Ectopic Expression ◽  
Receptor Potential ◽  
Temperature Sensing ◽  
Transient Receptor Potential Vanilloid ◽  
C Elegans ◽  
Trpv Channels ◽  
Warm Receptors ◽  
Transient Receptor

Abstract Caenorhabditis elegans (C. elegans) exhibits cold tolerance and temperature acclimatisation regulated by a small number of head sensory neurons, such as the ADL temperature-sensing neurons that express three transient receptor potential vanilloid (TRPV) channel subunits, OSM-9, OCR-2, and OCR-1. Here, we show that an OSM-9/OCR-2 regulates temperature acclimatisation and acts as an accessorial warmth-sensing receptor in ADL neurons. Caenorhabditis elegans TRPV channel mutants showed abnormal temperature acclimatisation. Ectopic expression of OSM-9 and OCR-2 in non-warming-responsive gustatory neurons in C. elegans and Xenopus oocytes revealed that OSM-9 and OCR-2 cooperatively responded to warming; however, neither TRPV subunit alone was responsive to warming. A warming-induced OSM-9/OCR-2-mediated current was detectable in Xenopus oocytes, yet ADL in osm-9 ocr-2 double mutant responds to warming; therefore, an OSM-9/OCR-2 TRPV channel and as yet unidentified temperature receptor might coordinate transmission of temperature signalling in ADL temperature-sensing neurons. This study demonstrates direct sensation of warming by TRPV channels in C. elegans.

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 The Contractile Phenotype of Skeletal Muscle in TRPV1 Knockout Mice Is Gender-Specific and Exercise-Dependent

Life ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 233
Author(s):  
Aude Lafoux ◽  
Sabine Lotteau ◽  
Corinne Huchet ◽  
Sylvie Ducreux
Keyword(s):  
Skeletal Muscle ◽  
Skeletal Muscles ◽  
Transient Receptor Potential ◽  
Heat Stroke ◽  
Receptor Potential ◽  
Muscle Physiology ◽  
Transient Receptor Potential Vanilloid ◽  
Noxious Heat ◽  
Contractile Phenotype ◽  
Transient Receptor

The transient receptor potential vanilloid 1 (TRPV1) belongs to the transient receptor potential superfamily of sensory receptors. TRPV1 is a non-selective cation channel permeable to Ca2+ that is capable of detecting noxious heat temperature and acidosis. In skeletal muscles, TRPV1 operates as a reticular Ca2+-leak channel and several TRPV1 mutations have been associated with two muscle disorders: malignant hyperthermia (MH) and exertional heat stroke (EHS). Although TRPV1−/− mice have been available since the 2000s, TRPV1’s role in muscle physiology has not been thoroughly studied. Therefore, the focus of this work was to characterize the contractile phenotype of skeletal muscles of TRPV1-deficient mice at rest and after four weeks of exercise. As MS and EHS have a higher incidence in men than in women, we also investigated sex-related phenotype differences. Our results indicated that, without exercise, TRPV1−/− mice improved in vivo muscle strength with an impairment of skeletal muscle in vitro twitch features, i.e., delayed contraction and relaxation. Additionally, exercise appeared detrimental to TRPV1−/− slow-twitch muscles, especially in female animals.

scholarly journals N-Arachidonoyl-l-Serine is Neuroprotective after Traumatic Brain Injury by Reducing Apoptosis

2011 ◽  
Vol 31 (8) ◽  
pp. 1768-1777 ◽  
Author(s):  
Ayelet Cohen-Yeshurun ◽  
Victoria Trembovler ◽  
Alexander Alexandrovich ◽  
Erik Ryberg ◽  
Peter J Greasley ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Specific Binding ◽  
Closed Head Injury ◽  
Receptor Potential ◽  
Bk Channels ◽  
Transient Receptor Potential Vanilloid ◽  
Lesion Volume ◽  
Protective Effects ◽  
Neuroprotective Effects ◽  
Trpv1 Channels

N-arachidonoyl-L-serine (AraS) is a brain component structurally related to the endocannabinoid family. We investigated the neuroprotective effects of AraS following closed head injury induced by weight drop onto the exposed fronto-parietal skull and the mechanisms involved. A single injection of AraS following injury led to a significant improvement in functional outcome, and to reduced edema and lesion volume compared with vehicle. Specific antagonists to CB2 receptors, transient receptor potential vanilloid 1 (TRPV1) or large conductance calcium-activated potassium (BK) channels reversed these effects. Specific binding assays did not indicate binding of AraS to the GPR55 cannabinoid receptor. N-arachidonoyl-l-serine blocked the attenuation in phosphorylated extracellular-signal-regulated kinase 1/2 (ERK) levels and led to an increase in pAkt in both the ipsilateral and contralateral cortices. Increased levels of the prosurvival factor Bcl-xL were evident 24 hours after injury in AraS-treated mice, followed by a 30% reduction in caspase-3 activity, measured 3 days after injury. Treatment with a CB2 antagonist, but not with a CB1 antagonist, reversed this effect. Our results suggest that administration of AraS leads to neuroprotection via ERK and Akt phosphorylation and induction of their downstream antiapoptotic pathways. These protective effects are related mostly to indirect signaling via the CB2R and TRPV1 channels but not through CB1 or GPR55 receptors.

Abstract 326: TRPV2 Regulates Cardiomyocyte Function via Altering Ca 2+ Cycling

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Xiaoqian Gao ◽  
Sheryl Koch ◽  
Min Jiang ◽  
Nathan Robbins ◽  
Wenfeng Cai ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Ventricular Myocytes ◽  
Receptor Potential ◽  
Ruthenium Red ◽  
Transient Receptor Potential Vanilloid ◽  
Dependent Manner ◽  
Noxious Heat ◽  
Cardiac Tissues ◽  
Membrane Stretching ◽  
Transient Receptor

TRPV2 is a member of transient receptor potential vanilloid (TRPV) family. As a Ca 2+ channel, it can detect various stimuli such as noxious heat (>52°C), membrane stretching, as well as a number of exogenous chemicals, including probenecid, 2-aminoethoxydiphenyl borate, and lysophospholipids. TRPV2 has been found in many tissue types, including neuron and kidney, but the function of TRPV2 in the heart is poorly understood. Here we show TRPV2 is involved in the Ca 2+ cycling process and then regulates the function of the cardiomyocyte. We identified the mRNA expression of TRPV2 in the cardiac tissues of mice using real-time PCR. By performing echocardiography we found that administration of probenecid, a selective TRPV2 agonist, increased cardiac ejection fraction in mice. This positive inotropic effect of probenecid was also shown in Langendorff perfused mice hearts as increased peak +dP/dt. In isolated ventricular myocytes, we found that probenecid significantly increased myocyte fractional shortening in a dose-dependent manner, which was fully blocked by ruthenium red, a non-selective TRPV2 blocker. We also performed fluorescent studies to examine myocyte Ca 2+ cycling. We found that probenecid significantly increased Ca 2+ transient and resting-state Ca 2+ sparks and this effect was eliminated by ruthenium red. When Ca 2+ storage in sarcoplasmic reticulum (SR) was depleted with caffeine, and SR Ca 2+ reuptake was blocked by thapsigargin at the same time, probenecid did not show any effects in either Ca 2+ transient or Ca 2+ sparks. Our patch clamp experiments indicate that probenecid treatment does not trigger any significant transmembrane Ca 2+ influx. These results point to the important role of TRPV2 in regulating SR Ca 2+ release. In conclusion, TRPV2 activation may contribute to increased SR Ca 2+ release, leading to the enhancement of myocyte contractility. Thus, TRPV2 plays a potentially important role in controlling the cellular function of heart.

TRPM channel function in Caenorhabditis elegans

2007 ◽  
Vol 35 (1) ◽  
pp. 129-132 ◽  
Author(s):  
H.A. Baylis ◽  
K. Goyal
Keyword(s):  
Caenorhabditis Elegans ◽  
Mammalian Cells ◽  
Transient Receptor Potential ◽  
Early Stage ◽  
Animal Experiments ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels ◽  
Growth Defect ◽  
C Elegans

The nematode Caenorhabditis elegans contains over 20 genes for TRP (transient receptor potential) channels which include members of all of the subclasses identified in mammalian cells. These proteins include three members of the TRPM (TRP melastatin) family: gon-2 (abnormal gonad development), gtl-1 (gon-2-like 1) and gtl-2. Although studies of these genes are at an early stage, we are beginning to understand their functions in the life of C. elegans. Mutations in gon-2 have defective gonad formation because of failures in the cell division of the somatic gonad precursor cells. gon-2 and gtl-1 are both expressed in the intestine of the animal. Experiments on gon-2,gtl-1 double mutants show that they have a severe growth defect that is ameliorated by the addition of high levels of Mg2+ to the growth medium. gon-2,gtl-1 double mutants have defective magnesium homoeostasis and also have altered sensitivity to toxic levels of Ni2+. Furthermore gon-2 mutants have reduced levels of IORCa (outwardly rectifying calcium current) in the intestinal cells. Thus these two channels appear to play an important role in cation homoeostasis in C. elegans. In addition, perturbing the function of gon-2 and gtl-1 disrupts the ultradian defecation rhythm in C. elegans, suggesting that these channels play an important role in regulating this calcium-dependent rhythmic process. The tractability of C. elegans as an experimental animal and its amenability to techniques such as RNAi (RNA interference) and in vivo imaging make it an excellent system for an integrative analysis of TRPM function.

scholarly journals Transient receptor potential vanilloid channels functioning in transduction of osmotic stimuli

2006 ◽  
Vol 191 (3) ◽  
pp. 515-523 ◽  
Author(s):  
Wolfgang Liedtke
Keyword(s):  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Evolutionary Conservation ◽  
Transient Receptor Potential Vanilloid ◽  
C Elegans ◽  
Trpv Channels ◽  
The Family ◽  
Osmotic Homeostasis ◽  
Transient Receptor ◽  
Osmotic Stimuli

In signal transduction of metazoan cells, ion channels of the family of transient receptor potential (TRP) have been identified to respond to diverse external and internal stimuli, amongst them osmotic stimuli. This review will highlight findings on the TRPV subfamily, both vertebrate and invertebrate members. Out of the six mammalian TRP vanilloid (TRPV) channels, TRPV1, TRPV2, and TRPV4 were demonstrated to function in transduction of osmotic stimuli. TRPV channels have been found to function in cellular as well as systemic osmotic homeostasis in vertebrates. Invertebrate TRPV channels, five in Caenorhabditis elegans and two in Drosophila, have been shown to play a role in mechanosensation, such as hearing and proprioception in Drosophila and nose touch in C. elegans, and in the response to osmotic stimuli in C. elegans. In a striking example of evolutionary conservation of function, mammalian TRPV4 has been found to rescue osmo-and mechanosensory deficits of the TRPV mutant strain osm-9 in C. elegans, despite not more than 26% orthology of the respective proteins.

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