• 제목/요약/키워드: TRPV2

검색결과 50건 처리시간 0.023초

Activation of the cGMP/Protein Kinase G Pathway by Nitric Oxide Can Decrease TRPV1 Activity in Cultured Rat Dorsal Root Ganglion Neurons

  • Jin, Yun-Ju;Kim, Jun;Kwak, Ji-Yeon
    • The Korean Journal of Physiology and Pharmacology
    • /
    • 제16권3호
    • /
    • pp.211-217
    • /
    • 2012
  • Recent studies have demonstrated that nitric oxide (NO) activates transient receptor potential vanilloid subtype 1 (TRPV1) via S-nitrosylation of the channel protein. NO also modulates various cellular functions via activation of the soluble guanylyl cyclase (sGC)/protein kinase G (PKG) pathway and the direct modification of proteins. Thus, in the present study, we investigated whether NO could indirectly modulate the activity of TRPV1 via a cGMP/PKG-dependent pathway in cultured rat dorsal root ganglion (DRG) neurons. NO donors, sodium nitroprusside (SNP) and S-nitro-N-acetylpenicillamine (SNAP), decreased capsaicin-evoked currents ($I_{cap}$). NO scavengers, hemoglobin and 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (CPTIO), prevented the inhibitory effect of SNP on $I_{cap}$. Membrane-permeable cGMP analogs, 8-bromoguanosine 3', 5'-cyclic monophosphate (8bromo-cGMP) and 8-(4chlorophenylthio)-guanosine 3',5'-cyclic monophosphate (8-pCPT-cGMP), and the guanylyl cyclase stimulator YC-1 mimicked the effect of SNP on $I_{cap}$. The PKG inhibitor KT5823 prevented the inhibition of $I_{cap}$ by SNP. These results suggest that NO can downregulate the function of TRPV1 through activation of the cGMP/PKG pathway in peripheral sensory neurons.

Analgesic and anti-inflammatory effects of galangin: a potential pathway to inhibit transient receptor potential vanilloid 1 receptor activation

  • Kaiwen Lin;Datian Fu;Zhongtao Wang;Xueer Zhang;Canyang Zhu
    • The Korean Journal of Pain
    • /
    • 제37권2호
    • /
    • pp.151-163
    • /
    • 2024
  • Background: Galangin, commonly employed in traditional Chinese medicine for its diverse medicinal properties, exhibits potential in treating inflammatory pain. Nevertheless, its mechanism of action remains unclear. Methods: Mice were randomly divided into 4 groups for 7 days: a normal control group, a galangin-treated (25 and 50 mg/kg), and a positive control celecoxib (20 mg/kg). Analgesic and anti-inflammatory effects were evaluated using a hot plate test, acetic acid-induced writhing test, acetic acid-induced vascular permeability test, formalin-induced paw licking test, and carrageenan-induced paw swelling test. The interplay between galangin, transient receptor potential vanilloid 1 (TRPV1), NF-κB, COX-2, and TNF-α proteins was evaluated via molecular docking. COX-2, PGE2, IL-1β, IL-6, and TNF-α levels in serum were measured using ELISA after capsaicin administration (200 nmol/L). TRPV1 expression in the dorsal root ganglion was analyzed by Western blot. The quantities of substance P (SP) and calcitonin gene-related peptide (CGRP) were assessed using qPCR. Results: Galangin reduced hot plate-induced licking latency, acetic acid-induced contortions, carrageenan-triggered foot inflammation, and capillary permeability in mice. It exhibited favorable affinity towards TRPV1, NF-κB, COX-2, and TNF-α, resulting in decreased levels of COX-2, PGE2, IL-1β, IL-6, and TNF-α in serum following capsaicin stimulation. Galangin effectively suppressed the upregulation of TRPV1 protein and associated receptor neuropeptides CGRP and SP mRNA, while concurrently inhibiting the expression of NF-κB, TNF-α, COX-2, and PGE2 mRNA. Conclusions: Galangin exerts its anti-inflammatory pain effects by inhibiting TRPV1 activation and regulating COX-2, NF-κB/TNF-α expression, providing evidence for the use of galangin in the management of inflammatory pain.

Expression of TRPV1 and iNOS in the Dorsal Root Ganglion Exposed by Autologous Nucleus Pulposus in the Rat

  • Kim, Su-Jeong;Seo, Jeong-Min;Cho, Yun-Woo;Park, Hea-Woon;Lee, Joon-Ha;Hwang, Se-Jin;Ahn, Sang-Ho
    • The Journal of Korean Physical Therapy
    • /
    • 제22권3호
    • /
    • pp.71-77
    • /
    • 2010
  • Purpose: To determine whether upregulation of inducible nitric oxide synthase (iNOS) transcription and translation is related to radicular pain in a model of lumbar disc herniation. Also, to investigate the temporal changes of mRNA expression of iNOS and the identity of iNOS and transient receptor potential vanilloid (TRPV) 1 channel expression cells in dorsal root ganglion (DRG) of a model of lumbar disc herniation. Methods: A lumbar disc herniated rat model was developed by implantation of the autologous nucleus pulposus, harvested from the coccygeal vertebra of each tail, on the left L5 nerve root just proximal to the DRG. Rats were tested for mechanical allodynia of the plantar surface of both hind paws 2 days before surgery and 1, 5, 10, 20 and 30 days postoperatively. Reverse transcription polymerase chain reaction (RT-PCR) was used to follow iNOS mRNA expression. To stain iNOS and TRPV1 in DRG, an immunohistochemical study was done 10 days after surgery. Results: A significant drop in mechanical withdrawal threshold on the ipsilateral and contralateral hind paws was observed 1 day after surgery and was prolonged to 30 days in rats with lumbar disc herniation. The expression of mRNA for iNOS peaked at postoperative day 10 on both sides of the DRG. iNOS-positive sensory neurons in the DRG varied in size from large to small diameter cells. A majority of small and intermediate sensory neurons were TRPV1-positive cells. Double immunofluorescence staining for TRPV1 and iNOS revealed that most intermediate TRPV1-positive sensory neurons co-localized with iNOS-positive neurons. Conclusion: Nucleus pulposus-induced mechanical allodynia can be generated without mechanical compression. This pain is related to temporal changes in expression of iNOS mRNA in the DRG. Co-localization of TRPV1 and iNOS in intermediate neurons of the DRG is correlated with pain modality and intensity.

두릅순 에탄올 추출물의 인간유래 피부각질형성세포와 피부섬유아세포에서의 자외선에 의한 광노화 억제효과 (Inhibitory effect of Aralia elata ethanol extract against skin damage in UVB-exposed human keratinocytes and human dermal fibroblasts)

  • 양지원;곽충실
    • Journal of Nutrition and Health
    • /
    • 제49권6호
    • /
    • pp.429-436
    • /
    • 2016
  • 본 연구에서는 피부의 표피와 진피에 분포하는 HaCaT 세포와 HDF 세포를 이용하여 항산화효과가 우수한 두릅순 추출물의 처리가 UVB에 의한 피부광노화를 억제할 수 있는지 알아보기 위하여 피부 염증반응과 관련한 사이토카인과 피부의 주요 구성 단백질인 collagen에 영향을 미칠 수 있는 MMP-1, type-I procollagen, TRPV-1 등의 단백질 발현에 미치는 영향을 분석하였다. HaCaT에 두릅순 추출물을 24시간 전처리한 경우 UVB ($55 mJ/cm^2$) 노출로 인해 증가한 염증매개인자인 IL-6, IL-8, $PGE_2$를 유의하게 감소시켰다. 또한, 피부 collagen의 정상적인 구조 및 양에 영향을 미치는 단백질들의 발현을 측정한 결과 HaCaT에서는 UVB 조사로 인해 증가한 TRPV-1과 MMP-1 단백질의 발현이 두릅순 에탄올 추출물의 전처리로 모두 감소하였고, HDF에서는 UVB를 조사한 대조군에 비하여 두릅순 추출물 처리가 MMP-1 단백질 발현을 감소시키는 동시에 collagen의 전구체인 type-I procollagen의 발현을 증가시키는 효과를 보였다. 이들 결과들로부터 항산화효과가 우수한 두릅순 70% 에탄올 추출물은 피부세포에서 UVB에 의한 염증반응을 억제시키는 동시에 피부 collagen의 감소를 억제시킴으로써 피부 광노화를 예방할 수 있는 천연 소재로 이용될 수 있다고 본다.

환도(GB30) 및 족삼리(ST36) 건강약침이 신경병증성 통증 유발 흰쥐에 미치는 영향 (Effects of Zingiberis Rhizoma Pharmacopuncture Injected at GB30 and ST36 on Neuropathic Pain in Rats)

  • 황민섭
    • Korean Journal of Acupuncture
    • /
    • 제36권1호
    • /
    • pp.52-62
    • /
    • 2019
  • Objectives : The objective of this study was to investigate the effects of Zingiberis Rhizoma Pharmacopuncture(ZP) at GB30 and ST36 in neuropathic pain induced SD rats by the block of Transient Receptor Potential Vanilloid 1(TRPV1). Methods : Neuropathic pain in rats was induced by tibial and common peroneal nerve transection of right leg. The rat subjects were divided into 6 groups : normal(Nor, n=5), control(Con, n=5), neuropathic pain plus 2 mg/kg ZP injection at GB30 and ST36(ZP-A, n=5), 10 mg/kg ZP(ZP-B, n=5), 20 mg/kg ZP(ZP-C, n=5) and 0.45 mg/kg Tramadol(Tra, n=5). Three days after the surgery, injections were administered once a day for 17 days. Withdrawal response of neuropathic rats' legs were measured by stimulating the paw of Right leg with von frey filament, acetone and radient heat on day 3, 7, 11, 15, 19 after surgery. After all treatments were completed, c-Fos in the midbrain central gray and TRPV1 & TRPA1 of DRG(L5) were analyzed. Results : Groups ZP-B and ZP-C showed a meaningful decrease in the withdrawal response of mechanical allodynia, thermal hyperalgesia and cold allodynia compared to the control group(p<0.05, p<0.01, p<0.001). Groups ZP-B and ZP-C showed a meaningful decrease in the expression of c-fos and TRPV1 protein level compared to the control group(p<0.05, p<0.01, p<0.001). Conclusions : These results suggest that Zingiberis Rhizoma Pharmacopuncture at GB30 and ST36 could decrease mechanical & cold allodynia and thermal hyperalgesia by block the TRPV1 on the model of neuropathic pain.

Cloning of a novel ion channel candidate by in silico gene mining

  • Shim, Won-Sik;Kim, Man-Su;Yang, Young-Duk;Park, Seung-Pyo;Kim, Byung-Moon;Oh, Uh-Taek
    • 대한약학회:학술대회논문집
    • /
    • 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
    • /
    • pp.192.2-193
    • /
    • 2003
  • Capsaicin, a pungent ingredient in chili pepper, is known to excite sensory neurons that mediate pain sensation. This effect of capsaicin is determined by unique receptors and the capsaicin receptor (transient receptor potential subfamily V, member 1 (TRPV1)) was cloned recently. TRPV1 contains six transmembrane domains and three ankyrin repeats at N-terminal. This characteristic architecture is common in other ion channel in TRPV families. (omitted)

  • PDF

Influence of $1{\alpha}$, 25-dihydroxyvitamin $D_3$ [1, $25(OH)_2D_3$] on the expression of Sox 9 and the transient receptor potential vanilloid 5/6 ion channels in equine articular chondrocytes

  • Hdud, Ismail M.;Loughna, Paul T.
    • Journal of Animal Science and Technology
    • /
    • 제56권8호
    • /
    • pp.33.1-33.8
    • /
    • 2014
  • Background: Sox 9 is a major marker of chondrocyte differentiation. When chondrocytes are cultured in vitro they progressively de-differentiate and this is associated with a decline in Sox 9 expression. The active form of vitamin D, 1, 25 $(OH)_2D_3$ has been shown to be protective of cartilage in both humans and animals. In this study equine articular chondrocytes were grown in culture and the effects of 1, 25 $(OH)_2D_3$ upon Sox 9 expression examined. The expression of the transient receptor potential vanilloid (TRPV) ion channels 5 and 6 in equine chondrocytes in vitro, we have previously shown, is inversely correlated with de-differentiation. The expression of these channels in response to 1, 25 $(OH)_2D_3$ administration was therefore also examined. Results: The active form of vitamin D (1, 25 $(OH)_2D_3$ when administered to cultured equine chondrocytes at two different concentrations significantly increased the expression of Sox 9 at both. In contrast 1, 25 $(OH)_2D_3$ had no significant effect upon the expression of either TRPV 5 or 6 at either the protein or the mRNA level. Conclusions: The increased expression of Sox 9, in equine articular chondrocytes in vitro, in response to the active form of vitamin D suggests that this compound could be utilized to inhibit the progressive de-differentiation that is normally observed in these cells. It is also supportive of previous studies indicating that $1{\alpha}$, 25-dihydroxyvitamin $D_3$ can have a protective effect upon cartilage in animals in vivo. The previously observed correlation between the degree of differentiation and the expression levels of TRPV 5/6 had suggested that these ion channels may have a direct involvement in, or be modulated by, the differentiation process in vitro. The data in the present study do not support this.

High dose of QX-314 produces anti-nociceptive effect without capsaicin in rats with inflammatory TMJ pain

  • Yang, Kui-Ye;Kim, Min-Su;Kim, Eun-Kyung;Kong, Mi-Sun;Ahn, Jong-Soo;Lee, Jong-Hun;Ju, Jin-Sook;Ahn, Dong-Kuk
    • International Journal of Oral Biology
    • /
    • 제38권4호
    • /
    • pp.135-140
    • /
    • 2013
  • 이상의 실험 결과들을 요약하면, 포르말린을 측두하악관절 내로 주입하여 발생한 염증성 통증 행위반응은 QX-314의 투여로 감소할 수 있었다. 저농도의 QX-314의 진통작용은 TRPV1 통로를 이용하여 세포막 내로 이동하여 작용이 나타났으며 고농도의 QX-314는 TRPV1 통로와 무관하게 진통작용을 나타내었다. 이와 같은 결과는 측두하악관절 장애로 인해 발생되는 염증성 통증에 QX-314가 효과적인 치료제로 사용할 수 있다는 것을 말해주며, 특히 고농도의 QX-314가 세포막을 이동하는 경로에 대한 연구가 더 진행된다면 임상에서 QX-314가 진통제로서 사용할 수 있는 계기가 될 것으로 판단된다.

The Effect of GCSB-5 a New Herbal Medicine on Changes in Pain Behavior and Neuroglial Activation in a Rat Model of Lumbar Disc Herniation

  • Cho, Hee Kyung;Kim, So-Yeon;Choi, Mi Jung;Baek, Seung Ok;Kwak, Sang Gyu;Ahn, Sang Ho
    • Journal of Korean Neurosurgical Society
    • /
    • 제59권2호
    • /
    • pp.98-105
    • /
    • 2016
  • Objective : Lumbar disc herniation can induce sciatica by mechanical compression and/or chemical irritation. The aim of this study was to compare the effects of GCSB-5 (Shinbaro$^{(R)}$) and NSAIDs on pain-related behavior and on the expressions of microglia, astrocytes, CGRP, TRPV1, IL-6, and CX3CL1 in a rat model of lumbar disc herniation. Methods : 112 male Sprague-Dawley rats underwent implantation of nucleus pulposus to a dorsal root ganglion (DRG). Rats were divided into five groups as follows; a saline group (the vehicle control group) (n=27), a 10 mg/kg aceclofenac group (the aceclofenac group) (n=22), and 100, 300 or 600 mg/kg GCSB-5 groups (the GCSB-5 100, 300, or 600 groups) (n=21 for each group). Rats were tested for mechanical allodynia at 3 days after surgery and at 1 day, 3 days, 7 days, 14 days, 21 days, 28 days, 35 days, 42 days, 49 days, and 56 days after treatment commencement. Immunohistochemical staining of microglia (Iba1), astrocytes (GFAP), CGRP, and TRPV1, and PCR for IL-6 and CX3CL1 were performed on spinal dorsal horns and DRGs at 56 days after medication commencement. Results : After 56 days of GCSB-5 300 administration, mechanical withdrawal thresholds were significantly increased (p<0.05), and immunohistochemical expressions of Iba1, GFAP, CGRP, and TRPV1 were reduced than other groups, but this difference was not statistically significant. Conclusion : These results indicate GCSB-5 reduces mechanical allodynia and downregulates neuroglial activity and the expressions of CGRP and TRPV1 in the spinal segments of a rat model of lumbar disc herniation.