scholarly journals Mast-Cell Degranulation Induced by Physical Stimuli Involves the Activation of Transient-Receptor-Potential Channel TRPV2

2012 ◽  
pp. 113-124 ◽  
Author(s):  
D. ZHANG ◽  
A. SPIELMANN ◽  
L. WANG ◽  
G. DING ◽  
F. HUANG ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Transient Receptor Potential ◽  
Laser Light ◽  
Receptor Potential ◽  
Ruthenium Red ◽  
Mast Cell Degranulation ◽  
Human Mast Cell ◽  
Physical Stimuli ◽  
Transient Receptor

A characteristic of mast cells is the degranulation in response to various stimuli. Here we have investigated the effects of various physical stimuli in the human mast-cell line HMC-1. We have shown that HMC-1 express the transient receptor potential channels TRPV1, TRPV2 and TRPV4. In the whole-cell patch-clamp configuration, increasing mechanical stress applied to the mast cell by hydrostatic pressure (–30 to –90 cm H2O applied via the patch pipette) induced a current that could be inhibited by 10 µM of ruthenium red. This current was also inhibited by 20 µM SKF96365, an inhibitor that is among TRPV channels specific for the TRPV2. A characteristic of TRPV2 is its activation by high noxious temperature; temperatures exceeding 50 °C induced a similar ruthenium-red-sensitive current. As another physical stimulus, we applied laser light of 640 nm. Here we have shown for the first time that the application of light (at 48 mW for 20 min) induced an SKF96365-sensitive current. All three physical stimuli that led to activation of SKF96365-sensitive current also induced pronounced degranulation in the mast cells, which could be blocked by ruthenium red or SKF96365. The results suggest that TRPV2 is activated by the three different types of physical stimuli. Activation of TRPV2 allows Ca2+ ions to enter the cell, which in turn will induce degranulation. We, therefore, suggest that TRPV2 plays a key role in mast-cell degranulation in response to mechanical, heat and red laser-light stimulation.

scholarly journals Functional Transient Receptor Potential Melastatin 7 Channels Are Critical for Human Mast Cell Survival

2007 ◽  
Vol 179 (6) ◽  
pp. 4045-4052 ◽  
Author(s):  
Rob C. E. Wykes ◽  
Moonhee Lee ◽  
S. Mark Duffy ◽  
Weidong Yang ◽  
Elizabeth P. Seward ◽  
...  
Keyword(s):  
Mast Cell ◽  
Cell Survival ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Human Mast Cell ◽  
Transient Receptor Potential Melastatin ◽  
Transient Receptor

scholarly journals Cutaneous Neuroimmune Interactions of TSLP and TRPV4 Play Pivotal Roles in Dry Skin-Induced Pruritus

2021 ◽  
Vol 12 ◽  
Author(s):  
Wook-Joo Lee ◽  
Won-Sik Shim
Keyword(s):  
Mast Cells ◽  
Dorsal Root ◽  
Transient Receptor Potential ◽  
Skin Barrier ◽  
Receptor Potential ◽  
Barrier Dysfunction ◽  
Dry Skin ◽  
Neuroimmune Interactions ◽  
Skin Conditions ◽  
Transient Receptor

Dry skin is a symptom of skin barrier dysfunction that evokes pruritus; however, the cutaneous neuroimmune interactions underlying dry skin-induced pruritus remain unclear. Therefore, we aimed to elucidate the mechanisms underlying dry skin-induced pruritus. To this end, an acetone/ethanol/water (AEW)-induced mouse model of dry skin was used in this study. We observed that the production of thymic stromal lymphopoietin (TSLP) significantly increased in the keratinocytes of AEW mice. Importantly, treatment with an antagonist of transient receptor potential cation channel subfamily V member 4 (TRPV4), HC067047, ameliorated dry skin conditions in AEW mice. The symptoms of dry skin were significantly reduced in Trpv4 knockout (KO) mice following treatment with AEW. The increase in the intracellular calcium levels by TSLP in the dorsal root ganglia (DRG) of Trpv4 KO mice was also significantly attenuated. The spontaneous scratching bouts were significantly decreased in both the HC067047-treated and Trpv4 KO AEW mice. Importantly, the TSLP-dependent release of tryptase from the mast cells was significantly reduced in both the HC067047-treated mice and Trpv4 KO AEW mice. Notably, inhibition of the TSLP-induced signaling pathway in DRG selectively reduced the spontaneous scratching bouts in AEW mice. Overall, the results demonstrated that the cutaneous neuroimmune interactions of TSLP and TRPV4 play pivotal roles in dry skin-induced pruritus.

PLA2 and TRPV4 channels regulate endothelial calcium in cerebral arteries

2007 ◽  
Vol 292 (3) ◽  
pp. H1390-H1397 ◽  
Author(s):  
Sean P. Marrelli ◽  
Roger G. O'Neil ◽  
Rachel C. Brown ◽  
Robert M. Bryan
Keyword(s):  
Transient Receptor Potential ◽  
Cerebral Arteries ◽  
Receptor Potential ◽  
Ruthenium Red ◽  
Transient Receptor Potential Vanilloid ◽  
Middle Cerebral Arteries ◽  
Trpv Channels ◽  
Intracellular Ca ◽  
Transient Receptor ◽  
Trpv4 Channel

We previously demonstrated that endothelium-derived hyperpolarizing factor (EDHF)-mediated dilations in cerebral arteries are significantly reduced by inhibitors of PLA2. In this study we examined possible mechanisms by which PLA2 regulates endothelium-dependent dilation, specifically whether PLA2 is involved in endothelial Ca2+ regulation through stimulation of TRPV4 channels. Studies were carried out with middle cerebral arteries (MCA) or freshly isolated MCA endothelial cells (EC) of male Long-Evans rats. Nitro-l-arginine methyl ester (l-NAME) and indomethacin were present throughout. In pressurized MCA, luminally delivered UTP produced increased EC intracellular Ca2+ concentration ([Ca2+]i) and MCA dilation. Incubation with PACOCF3, a PLA2 inhibitor, significantly reduced both EC [Ca2+]i and dilation responses to UTP. EC [Ca2+]i was also partially reduced by a transient receptor potential vanilloid (TRPV) channel blocker, ruthenium red. Manganese quenching experiments demonstrated Ca2+ influx across the luminal and abluminal face of the endothelium in response to UTP. Interestingly, PLA2-sensitive Ca2+ influx occurred primarily across the abluminal face. Luminal application of arachidonic acid, the primary product of PLA2 and a demonstrated activator of certain TRPV channels, increased both EC [Ca2+]i and MCA diameter. TRPV4 mRNA and protein was demonstrated in the endothelium by RT-PCR and immunofluorescence, respectively. Finally, application of 4α-phorbol 12,13-didecanoate (4αPDD), a TRPV4 channel activator, produced an increase in EC [Ca2+]i that was significantly reduced in the presence of ruthenium red. We conclude that PLA2 is involved in EC Ca2+ regulation through its regulation of TRPV4 channels. Furthermore, the PLA2-sensitive component of Ca2+ influx may be polarized to the abluminal face of the endothelium.

Thermal sensitivity of isolated vagal pulmonary sensory neurons: role of transient receptor potential vanilloid receptors

2006 ◽  
Vol 291 (3) ◽  
pp. R541-R550 ◽  
Author(s):  
Dan Ni ◽  
Qihai Gu ◽  
Hong-Zhen Hu ◽  
Na Gao ◽  
Michael X. Zhu ◽  
...  
Keyword(s):  
Sensory Neurons ◽  
Transient Receptor Potential ◽  
Thermal Sensitivity ◽  
Receptor Potential ◽  
Ruthenium Red ◽  
Transient Receptor Potential Vanilloid ◽  
Temperature Sensitive ◽  
Inward Current ◽  
Transient Receptor ◽  
Increasing Temperature

A recent study has demonstrated that increasing the intrathoracic temperature from 36°C to 41°C induced a distinct stimulatory and sensitizing effect on vagal pulmonary C-fiber afferents in anesthetized rats ( J Physiol 565: 295–308, 2005). We postulated that these responses are mediated through a direct activation of the temperature-sensitive transient receptor potential vanilloid (TRPV) receptors by hyperthermia. To test this hypothesis, we studied the effect of increasing temperature on pulmonary sensory neurons that were isolated from adult rat nodose/jugular ganglion and identified by retrograde labeling, using the whole cell perforated patch-clamping technique. Our results showed that increasing temperature from 23°C (or 35°C) to 41°C in a ramp pattern evoked an inward current, which began to emerge after exceeding a threshold of ∼34.4°C and then increased sharply in amplitude as the temperature was further increased, reaching a peak current of 173 ± 27 pA ( n = 75) at 41°C. The temperature coefficient, Q10, was 29.5 ± 6.4 over the range of 35–41°C. The peak inward current was only partially blocked by pretreatment with capsazepine (Δ I = 48.1 ± 4.7%, n = 11) or AMG 9810 (Δ I = 59.2 ± 7.8%, n = 8), selective antagonists of the TRPV1 channel, but almost completely abolished (Δ I = 96.3 ± 2.3%) by ruthenium red, an effective blocker of TRPV1–4 channels. Furthermore, positive expressions of TRPV1–4 transcripts and proteins in these neurons were demonstrated by RT-PCR and immunohistochemistry experiments, respectively. On the basis of these results, we conclude that increasing temperature within the normal physiological range can exert a direct stimulatory effect on pulmonary sensory neurons, and this effect is mediated through the activation of TRPV1, as well as other subtypes of TRPV channels.

scholarly journals Camphor, Applied Epidermally to the Back, Causes Snout- and Chest-Grooming in Rats: A Response Mediated by Cutaneous TRP Channels

2019 ◽  
Vol 12 (1) ◽  
pp. 24
Author(s):  
Débora Ishikawa ◽  
Robson Vizin ◽  
Cristiane Souza ◽  
Daniel Carrettiero ◽  
Andrej Romanovsky ◽  
...  
Keyword(s):  
Wistar Rats ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Ruthenium Red ◽  
The Self ◽  
Grooming Behavior ◽  
Behavioral Defense ◽  
Male Wistar Rats ◽  
Transient Receptor

Thermoregulatory grooming, a behavioral defense against heat, is known to be driven by skin-temperature signals. Because at least some thermal cutaneous signals that drive heat defenses are likely to be generated by transient receptor potential (TRP) channels, we hypothesized that warmth-sensitive TRPs drive thermoregulatory grooming. Adult male Wistar rats were used. We showed that camphor, a nonselective agonist of several TRP channels, including vanilloid (V) 3, when applied epidermally to the back (500 mg/kg), caused a pronounced self-grooming response, including paw-licking and snout- and chest-“washing”. By the percentage of time spent grooming, the response was similar to the thermoregulatory grooming observed during exposure to ambient warmth (32 °C). Ruthenium red (a non-selective antagonist of TRP channels, including TRPV3), when administered intravenously at a dose of 0.1 mg/kg, attenuated the self-grooming behavior induced by either ambient warmth or epidermal camphor. Furthermore, the intravenous administration of AMG8432 (40 mg/kg), a relatively selective TRPV3 antagonist, also attenuated the self-grooming response to epidermal camphor. We conclude that camphor causes the self-grooming behavior by acting on TRP channels in the skin. We propose that cutaneous warmth signals mediated by TRP channels, possibly including TRPV3, drive thermoregulatory self-grooming in rats.

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.

scholarly journals Essential Role of Mast Cells in the Visceral Hyperalgesia Induced byT. spiralisInfection and Stress in Rats

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Chang-Qing Yang ◽  
Yan-Yu Wei ◽  
Chan-Juan Zhong ◽  
Li-Ping Duan
Keyword(s):  
Mast Cells ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Pcr Analysis ◽  
Signal Pathways ◽  
Transient Receptor Potential Vanilloid ◽  
Visceral Hyperalgesia ◽  
Cold Restraint Stress ◽  
Transient Receptor ◽  
Extracellular Regulated Kinase

Mast cells (MCs) deficient rats (Ws/Ws) were used to investigate the roles of MCs in visceral hyperalgesia. Ws/Ws and wild control (+/+) rats were exposed toT. spiralisor submitted to acute cold restraint stress (ACRS). Levels of proteinase-activated receptor 2 (PAR2) and nerve growth factor (NGF) were determined by immunoblots and RT-PCR analysis, and the putative signal pathways including phosphorylated extracellular-regulated kinase (pERK1/2) and transient receptor potential vanilloid receptor 1 (TRPV1) were further identified. Visceral hyperalgesia triggered by ACRS was observed only in+/+rats. The increased expression of PAR2 and NGF was observed only in+/+rats induced byT. spiralisand ACRS. The activation of pERK1/2 induced by ACRS occurred only in+/+rats. However, a significant increase of TRPV1 induced byT. spiralisand ACRS was observed only in+/+rats. The activation of PAR2 and NGF via both TRPV1 and pERK1/2 signal pathway is dependent on MCs in ACRS-induced visceral hyperalgesia rats.

scholarly journals ATP Release from Mast Cells by Physical Stimulation: A Putative Early Step in Activation of Acupuncture Points

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Lina Wang ◽  
Jacek Sikora ◽  
Lei Hu ◽  
Xueyong Shen ◽  
Ryszard Grygorczyk ◽  
...  
Keyword(s):  
Mast Cells ◽  
Mechanical Stress ◽  
Laser Light ◽  
Atp Release ◽  
Laser Acupuncture ◽  
Human Mast Cell ◽  
Acupuncture Points ◽  
Hypotonic Solution ◽  
Physical Stimulation ◽  
Physical Stimuli

In Chinese medicine acupuncture points are treated by physical stimuli to counteract various diseases. These stimuli include mechanical stress as applied during the needle manipulation or tuina, high temperatures as applied during moxibustion, and red laser light applied during laser acupuncture. This study aimed to investigate cellular responses to stimuli that might occur in the tissue of acupuncture points. Since they have a characteristically high density of mast cells that degranulate in response to acupuncture, we asked whether these processes lead to ATP release. We tested inin vitroexperiments on mast cells of the human mast-cell line HMC-1 the effects of the physical stimuli; mechanical stress was applied by superfusion of the cells with hypotonic solution, heat was applied by incubation of the cells at 52°C, and red laser light of 657 nm was used for irradiation. We demonstrate that all the stimuli induce ATP release from model human mast HMC-1 cells, and this release is associated with an intracellular free Ca2+rise. We hypothesize that ATP released from mast cells supplements the already known release of ATP from keratinocytes and, by acting on P2X receptors, it may serve as initial mediator of acupuncture-induced analgesia.

scholarly journals TRPV4 activation mediates flow-induced nitric oxide production in the rat thick ascending limb

2014 ◽  
Vol 307 (6) ◽  
pp. F666-F672 ◽  
Author(s):  
Pablo D. Cabral ◽  
Jeffrey L. Garvin
Keyword(s):  
Nitric Oxide ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Ruthenium Red ◽  
Transient Receptor Potential Vanilloid ◽  
No Production ◽  
Thick Ascending Limb ◽  
Different Types ◽  
Luminal Flow ◽  
Transient Receptor

Nitric oxide (NO) regulates renal function. Luminal flow stimulates NO production in the thick ascending limb (TAL). Transient receptor potential vanilloid 4 (TRPV4) is a mechano-sensitive channel activated by luminal flow in different types of cells. We hypothesized that TRPV4 mediates flow-induced NO production in the rat TAL. We measured NO production in isolated, perfused rat TALs using the fluorescent dye DAF FM. Increasing luminal flow from 0 to 20 nl/min stimulated NO from 8 ± 3 to 45 ± 12 arbitrary units (AU)/min ( n = 5; P < 0.05). The TRPV4 antagonists, ruthenium red (15 μmol/l) and RN 1734 (10 μmol/l), blocked flow-induced NO production. Also, luminal flow did not increase NO production in the absence of extracellular calcium. We also studied the effect of luminal flow on NO production in TALs transduced with a TRPV4shRNA. In nontransduced TALs luminal flow increased NO production by 47 ± 17 AU/min ( P < 0.05; n = 5). Similar to nontransduced TALs, luminal flow increased NO production by 39 ± 11 AU/min ( P < 0.03; n = 5) in TALs transduced with a control negative sequence-shRNA while in TRPV4shRNA-transduced TALs, luminal flow did not increase NO production (Δ10 ± 15 AU/min; n = 5). We then tested the effect of two different TRPV4 agonists on NO production in the absence of luminal flow. 4α-Phorbol 12,13-didecanoate (1 μmol/l) enhanced NO production by 60 ± 11 AU/min ( P < 0.002; n = 7) and GSK1016790A (10 ηmol/l) increased NO production by 52 ± 15 AU/min ( P < 0.03; n = 5). GSK1016790A (10 ηmol/l) did not stimulate NO production in TRPV4shRNA-transduced TALs. We conclude that activation of TRPV4 channels mediates flow-induced NO production in the rat TAL.

Functional Expression of an Osmosensitive Cation Channel, Transient Receptor Potential Vanilloid 4, in Rat Vestibular Ganglia

2016 ◽  
Vol 21 (4) ◽  
pp. 268-274 ◽  
Author(s):  
Takefumi Kamakura ◽  
Makoto Kondo ◽  
Yoshihisa Koyama ◽  
Yukiko Hanada ◽  
Yusuke Ishida ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Functional Expression ◽  
Ruthenium Red ◽  
Cation Channel ◽  
Trigeminal Ganglia ◽  
Transient Receptor Potential Vanilloid ◽  
Trpv Channels ◽  
Polymerase Chain ◽  
Transient Receptor

Transient receptor potential vanilloid (TRPV) 4 is a nonselective cation channel expressed in sensory neurons such as those in the dorsal root and trigeminal ganglia, kidney, and inner ear. TRPV4 is activated by mechanical stress, heat, low osmotic pressure, low pH, and phorbol derivatives such as 4α-phorbol 12,13-didecanoate (4α-PDD). We investigated the expression of TRPV4 in rat vestibular ganglion (VG) neurons. The TRPV4 gene was successfully amplified from VG neuron mRNA using reverse-transcription polymerase chain reaction. Furthermore, immunoblotting showed positive expression of TRPV4 protein in VG neurons. Immunohistochemistry indicated that TRPV4 was localized predominantly on the plasma membrane of VG neurons. Calcium (Ca2+) imaging of VG neurons showed that 4α-PDD and/or hypotonic stimuli caused an increase in intracellular Ca2+ concentration ([Ca2+]i) that was almost completely inhibited by ruthenium red, a selective antagonist of TRPV channels. Interestingly, a [Ca2+]i increase was evoked by both hypotonic stimuli and 4α-PDD in approximately 38% of VG neurons. These data indicate that TRPV4 is functionally expressed in VG neurons as an ion channel and that TRPV4 likely participates in VG neurons for vestibular neurotransmission as an osmoreceptor and/or mechanoreceptor.

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