scholarly journals TRPV1 induction in airway vagal low-threshold mechanosensory neurons by allergen challenge and neurotrophic factors

2012 ◽  
Vol 302 (9) ◽  
pp. L941-L948 ◽  
Author(s):  
Tina Marie Lieu ◽  
Allen C. Myers ◽  
Sonya Meeker ◽  
Bradley J. Undem
Keyword(s):  
Mrna Expression ◽  
Neurotrophic Factor ◽  
Transient Receptor Potential ◽  
De Novo ◽  
Allergen Challenge ◽  
Pcr Analysis ◽  
Phenotypic Change ◽  
Transient Receptor Potential Vanilloid ◽  
Trpv1 Channels ◽  
Low Threshold

We addressed the hypothesis that allergic inflammation in guinea pig airways leads to a phenotypic switch in vagal tracheal cough-causing, low-threshold mechanosensitive Aδ neurons, such that they begin expressing functional transient receptor potential vanilloid (TRPV1) channels. Guinea pigs were actively sensitized to ovalbumin (OVA) and beginning 21 days later exposed via aerosol to OVA daily for 3 days. Tracheal-specific neurons were identified in the nodose ganglion using retrograde tracing techniques. Tracheal specific neurons were isolated, and mRNA expression was evaluated at the single-neuron level using RT-PCR analysis. Electrophysiological studies have revealed that the vast majority of vagal nodose afferent nerves innervating the trachea are capsaicin-insensitive Aδ-fibers. Consistent with this, we found <20% of these neurons express TRPV1 mRNA or respond to capsaicin in a calcium assay. Allergen exposure induced de novo TRPV1 mRNA in a majority of the tracheal-specific nodose neurons ( P < 0.05). The allergen-induced TRPV1 induction was mimicked by applying either brain-derived neurotrophic factor (BDNF) or glial-derived neurotrophic factor (GDNF) to the tracheal lumen. The BDNF-induced phenotypic change observed at the level of mRNA expression was mimicked using a calcium assay to assess functional TRPV1 ion channels. Finally, OVA exposure induced BDNF and GDNF production in the tracheal epithelium, the immediate vicinity of the nodose Aδ -fibers terminations. The induction of TRPV1 in nodose tracheal Aδ -fibers would substantively expand the nature of stimuli capable of activating these cough-causing nerves.

scholarly journals Identification and Quantification of Transient Receptor Potential Vanilloid 1 (TRPV1) in Equine Articular Tissue

Animals ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 506
Author(s):  
Anne Frank Gallagher vom Braucke ◽  
Nanna Lysemose Frederiksen ◽  
Lise Charlotte Berg ◽  
Stacie Aarsvold ◽  
Felix Christoph Müller ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Synovial Tissue ◽  
Joint Pain ◽  
Transient Receptor Potential ◽  
Symptomatic Relief ◽  
T Test ◽  
Pcr Analysis ◽  
Transient Receptor Potential Vanilloid ◽  
Expression Ratio ◽  
Necrosis Factor Alpha

Joint pain and osteoarthritis (OA) are some of the most common causes of lameness in horses, and most of the available treatments focus on symptomatic relief without a disease-modifying effect. TRPV1 is a potential target for treating joint diseases, including OA, and the present study aims to investigate if the TRPV1 receptor is present in equine articular tissue and determine whether the number of receptors is upregulated in joint inflammation. Metacarpo/metatarsophalangeal (MCP/MTP) joints from 15 horses euthanised for reasons unrelated to this study were included. Based on synovial fluid analysis, macroscopic evaluation, and magnetic resonance imaging (MRI), joints were divided into two groups: healthy joints and joints with pathology. ELISA analysis was performed on synovial tissue harvested from all joints. TPRV1 was found in all joints. The mean concentration of TRPV1 compared to total protein in healthy joints (8.4 × 10−7 ng/mL) and joints with pathology (12.9 × 10−7 ng/mL) differed significantly (p = 0.01, t-test with Welch correction). Quantitative real-time reverse transcriptase PCR analysis was performed on RNA isolates from synovial tissue from all joints. TRPV1 mRNA expression ratio normalized to glyceraldehyde 3-phosphate dehydrogenase (GAPDH) in healthy joints (0.16 (SD: 0.19)) and joints with pathology (0.24 (SD: 0.14)) did not differ significantly (p = 0.43, t-test with Welch correction). mRNA expression of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) was very low for both groups. In conclusion, TRPV1 was detected both on mRNA and the protein level, with a higher expression of TRPV1 in samples from joints with pathology. Future studies will determine the clinical potential of equine TRPV1 as a target in the management of joint pain and inflammation.

scholarly journals Interactions between Chemesthesis and Taste: Role of TRPA1 and TRPV1

2021 ◽  
Vol 22 (7) ◽  
pp. 3360
Author(s):  
Mee-Ra Rhyu ◽  
Yiseul Kim ◽  
Vijay Lyall
Keyword(s):  
Transient Receptor Potential ◽  
Taste Receptor ◽  
Sensory Nerve ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Trpv1 Channels ◽  
Trigeminal Neurons ◽  
Calcitonin Gene ◽  
Transient Receptor

In addition to the sense of taste and olfaction, chemesthesis, the sensation of irritation, pungency, cooling, warmth, or burning elicited by spices and herbs, plays a central role in food consumption. Many plant-derived molecules demonstrate their chemesthetic properties via the opening of transient receptor potential ankyrin 1 (TRPA1) and transient receptor potential vanilloid 1 (TRPV1) channels. TRPA1 and TRPV1 are structurally related thermosensitive cation channels and are often co-expressed in sensory nerve endings. TRPA1 and TRPV1 can also indirectly influence some, but not all, primary taste qualities via the release of substance P and calcitonin gene-related peptide (CGRP) from trigeminal neurons and their subsequent effects on CGRP receptor expressed in Type III taste receptor cells. Here, we will review the effect of some chemesthetic agonists of TRPA1 and TRPV1 and their influence on bitter, sour, and salt taste qualities.

scholarly journals Permeation and block of TRPV1 channels by the cationic lidocaine derivative QX-314

2013 ◽  
Vol 109 (7) ◽  
pp. 1704-1712 ◽  
Author(s):  
Michelino Puopolo ◽  
Alexander M. Binshtok ◽  
Gui-Lan Yao ◽  
Seog Bae Oh ◽  
Clifford J. Woolf ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Neuronal Cell ◽  
Reversal Potential ◽  
Dorsal Root Ganglion Neurons ◽  
C6 Glioma Cells ◽  
Transient Receptor Potential Vanilloid ◽  
Trpv1 Channels ◽  
Inward Currents ◽  
Pore Dilation ◽  
Ganglion Neurons

QX-314 ( N-ethyl-lidocaine) is a cationic lidocaine derivative that blocks voltage-dependent sodium channels when applied internally to axons or neuronal cell bodies. Coapplication of external QX-314 with the transient receptor potential vanilloid 1 protein (TRPV1) agonist capsaicin produces long-lasting sodium channel inhibition in TRPV1-expressing neurons, suggestive of QX-314 entry into the neurons. We asked whether QX-314 entry occurs directly through TRPV1 channels or through a different pathway (e.g., pannexin channels) activated downstream of TRPV1 and whether QX-314 entry requires the phenomenon of “pore dilation” previously reported for TRPV1. With external solutions containing 10 or 20 mM QX-314 as the only cation, inward currents were activated by stimulation of both heterologously expressed and native TRPV1 channels in rat dorsal root ganglion neurons. QX-314-mediated inward current did not require pore dilation, as it activated within several seconds and in parallel with Cs-mediated outward current, with a reversal potential consistent with PQX-314/ PCs = 0.12. QX-314-mediated current was no different when TRPV1 channels were expressed in C6 glioma cells, which lack expression of pannexin channels. Rapid addition of QX-314 to physiological external solutions produced instant partial inhibition of inward currents carried by sodium ions, suggesting that QX-314 is a permeant blocker. Maintained coapplication of QX-314 with capsaicin produced slowly developing reduction of outward currents carried by internal Cs, consistent with intracellular accumulation of QX-314 to concentrations of 50–100 μM. We conclude that QX-314 is directly permeant in the “standard” pore formed by TRPV1 channels and does not require either pore dilation or activation of additional downstream channels for entry.

scholarly journals Inhibition of Microglia-Derived Oxidative Stress by Ciliary Neurotrophic Factor Protects Dopamine Neurons In Vivo from MPP+ Neurotoxicity

2018 ◽  
Vol 19 (11) ◽  
pp. 3543 ◽  
Author(s):  
Jeong Baek ◽  
Jae Jeong ◽  
Kyoung Kim ◽  
So-Yoon Won ◽  
Young Chung ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurotrophic Factor ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Ciliary Neurotrophic Factor ◽  
Dopamine Neurons ◽  
Transient Receptor Potential Vanilloid

We demonstrated that capsaicin (CAP), an agonist of transient receptor potential vanilloid subtype 1 (TRPV1), inhibits microglia activation and microglia-derived oxidative stress in the substantia nigra (SN) of MPP+-lesioned rat. However, the detailed mechanisms how microglia-derived oxidative stress is regulated by CAP remain to be determined. Here we report that ciliary neurotrophic factor (CNTF) endogenously produced by CAP-activated astrocytes through TRPV1, but not microglia, inhibits microglial activation and microglia-derived oxidative stress, as assessed by OX-6 and OX-42 immunostaining and hydroethidine staining, respectively, resulting in neuroprotection. The significant increase in levels of CNTF receptor alpha (CNTFRα) expression was evident on microglia in the MPP+-lesioned rat SN and the observed beneficial effects of CNTF was abolished by treatment with CNTF receptor neutralizing antibody. It is therefore likely that CNTF can exert its effect via CNTFRα on microglia, which rescues dopamine neurons in the SN of MPP+-lesioned rats and ameliorates amphetamine-induced rotations. Immunohistochemical analysis revealed also a significantly increased expression of CNTFRα on microglia in the SN from human Parkinson’s disease patients compared with age-matched controls, indicating that these findings may have relevance to the disease. These data suggest that CNTF originated from TRPV1 activated astrocytes may be beneficial to treat neurodegenerative disease associated with neuro-inflammation such as Parkinson’s disease.

scholarly journals TRPV1 channels and the progesterone receptor Sig-1R interact to regulate pain

2018 ◽  
Vol 115 (7) ◽  
pp. E1657-E1666 ◽  
Author(s):  
Miguel Ortíz-Rentería ◽  
Rebeca Juárez-Contreras ◽  
Ricardo González-Ramírez ◽  
León D. Islas ◽  
Félix Sierra-Ramírez ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Sigma 1 Receptor ◽  
Trpv1 Channels ◽  
Nociceptive Responses ◽  
Sigma 1 ◽  
Transient Receptor ◽  
Thermal Stimuli

The Transient Receptor Potential Vanilloid 1 (TRPV1) ion channel is expressed in nociceptors where, when activated by chemical or thermal stimuli, it functions as an important transducer of painful and itch-related stimuli. Although the interaction of TRPV1 with proteins that regulate its function has been previously explored, their modulation by chaperones has not been elucidated, as is the case for other mammalian TRP channels. Here we show that TRPV1 physically interacts with the Sigma 1 Receptor (Sig-1R), a chaperone that binds progesterone, an antagonist of Sig-1R and an important neurosteroid associated to the modulation of pain. Antagonism of Sig-1R by progesterone results in the down-regulation of TRPV1 expression in the plasma membrane of sensory neurons and, consequently, a decrease in capsaicin-induced nociceptive responses. This is observed both in males treated with a synthetic antagonist of Sig-1R and in pregnant females where progesterone levels are elevated. This constitutes a previously undescribed mechanism by which TRPV1-dependent nociception and pain can be regulated.

scholarly journals Activation of TRPV1 channels leads to stimulation of NKCC1 cotransport in the lens

2018 ◽  
Vol 315 (6) ◽  
pp. C793-C802 ◽  
Author(s):  
Mohammad Shahidullah ◽  
Amritlal Mandal ◽  
Nicholas A. Delamere
Keyword(s):  
Ion Transport ◽  
Transient Receptor Potential ◽  
Ion Homeostasis ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Signaling Mechanism ◽  
Trpv1 Channels ◽  
Trpv1 Antagonist ◽  
Transient Receptor ◽  
Stimulation Of

Lens ion homeostasis is crucial in maintaining water content and, in turn, refractive index and transparency of the multicellular syncytium-like structure. New information is emerging on the regulation of ion transport in the lens by mechanisms that rely on transient receptor potential vanilloid (TRPV) ion channels. We found recently that TRPV1 activation leads to Ca2+/PKC-dependent ERK1/2 signaling. Here, we show that the TRPV1 agonist capsaicin (100 nM) and hyperosmotic solution (350 vs. 300 mosM) each caused an increase of bumetanide-inhibitable Rb uptake by intact porcine lenses and Na-K-2Cl cotransporter 1 (NKCC1) phosphorylation in the lens epithelium. The TRPV1 antagonist A889425 (1 µM) abolished the increases of Rb uptake and NKCC1 phosphorylation in response to hyperosmotic solution. Exposing lenses to hyperosmotic solution in the presence of MEK/ERK inhibitor U0126 (10 µM) or the with-no-lysine kinase (WNK) inhibitor WNK463 (1 µM) also prevented NKCC1 phosphorylation and the Rb uptake responses to hyperosmotic solution. WNK463 did not prevent the increase in ERK1/2 phosphorylation that occurs in response to capsaicin or hyperosmotic solution, suggesting that ERK1/2 activation occurs before WNK activation in the sequence of signaling events. Taken together, the evidence indicates that activation of TRPV1 is a critical early step in a signaling mechanism that responds to a hyperosmotic stimulus, possibly lens shrinkage. By activating ERK1/2 and WNK, TRPV1 activation leads to NKCC1 phosphorylation and stimulation of NKCC1-mediated ion transport.

scholarly journals Pore Helix Domain Is Critical to Camphor Sensitivity of Transient Receptor Potential Vanilloid 1 Channel

2012 ◽  
Vol 116 (4) ◽  
pp. 903-917 ◽  
Author(s):  
Lenka Marsakova ◽  
Filip Touska ◽  
Jan Krusek ◽  
Viktorie Vlachova
Keyword(s):  
Spatial Distribution ◽  
Plasma Membranes ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Structural Basis ◽  
Transient Receptor Potential Vanilloid ◽  
Trpv1 Channel ◽  
Patch Clamp Technique ◽  
Trpv1 Channels ◽  
Transient Receptor

Background The recent discovery that camphor activates and strongly desensitizes the capsaicin-sensitive and noxious heat-sensitive channel transient receptor potential vanilloid subfamily member 1 (TRPV1) has provided new insights and opened up new research paths toward understanding why this naturally occurring monoterpene is widely used in human medicine for its local counter-irritant, antipruritic, and anesthetic properties. However, the molecular basis for camphor sensitivity remains mostly unknown. The authors attempt to explore the nature of the activation pathways evoked by camphor and narrow down a putative interaction site at TRPV1. Methods The authors transiently expressed wild-type or specifically mutated recombinant TRPV1 channels in human embryonic kidney cells HEK293T and recorded cation currents with the whole cell, patch clamp technique. To monitor changes in the spatial distribution of phosphatidylinositol 4,5-bisphosphate, they used fluorescence resonance energy transfer measurements from cells transfected with the fluorescent protein-tagged pleckstrin homology domains of phospholipase C. Results The results revealed that camphor modulates TRPV1 channel through the outer pore helix domain by affecting its overall gating equilibrium. In addition, camphor, which generally is known to decrease the fluidity of cell plasma membranes, may also regulate the activity of TRPV1 by inducing changes in the spatial distribution of phosphatidylinositol-4,5-bisphosphate on the inner leaflet of the plasma membrane. Conclusions The findings of this study provide novel insights into the structural basis for the modulation of TRPV1 channel by camphor and may provide an explanation for the mechanism by which camphor modulates thermal sensation in vivo.

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