• 제목/요약/키워드: TRPV1 receptor

검색결과 52건 처리시간 0.023초

Combination of a Rapidly Penetrating Agonist and a Slowly Penetrating Antagonist Affords Agonist Action of Limited Duration at the Cellular Level

  • Pearce, Larry V.;Ann, Jihyae;Blumberg, Peter M.;Lee, Jeewoo
    • Biomolecules & Therapeutics
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    • 제27권5호
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    • pp.435-441
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    • 2019
  • The capsaicin receptor TRPV1 (transient receptor potential vanilloid 1) has been an object of intense interest for pharmacological development on account of its critical role in nociception. In the course of structure activity analysis, it has become apparent that TRPV1 ligands may vary dramatically in the rates at which they interact with TRPV1, presumably reflecting differences in their abilities to penetrate into the cell. Using a fast penetrating agonist together with an excess of a slower penetrating antagonist, we find that we can induce an agonist response of limited duration and, moreover, the duration of the agonist response remains largely independent of the absolute dose of agonist, as long as the ratio of antagonist to agonist is held constant. This general approach for limiting agonist duration under conditions in which absolute agonist dose is variable should have more general applicability.

Repeated Morphine Administration Increases TRPV1 mRNA Expression and Autoradiographic Binding at Supraspinal Sites in the Pain Pathway

  • Nguyen, Thi-Lien;Nam, Yun-Son;Lee, Seok-Yong;Jang, Choon-Gon
    • Biomolecules & Therapeutics
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    • 제30권4호
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    • pp.328-333
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    • 2022
  • Repeated morphine administration induces tolerance to its analgesic effects. A previous study reported that repeated morphine treatment activates transient receptor potential vanilloid type 1 (TRPV1) expression in the sciatic nerve, dorsal root ganglion, and spinal cord, contributing to morphine tolerance. In the present study, we analyzed TRPV1 expression and binding sites in supraspinal pain pathways in morphine-tolerant mice. The TRPV1 mRNA levels and binding sites were remarkably increased in the cortex and thalamus of these animals. Our data provide additional insights into the effects of morphine on TRPV1 in the brain and suggest that changes in the expression of, and binding to TRPV1 in the brain are involved in morphine tolerance.

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
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    • 제37권2호
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    • pp.151-163
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    • 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.

Antipruritic effect of curcumin on histamine-induced itching in mice

  • Lee, Han Kyu;Park, Seok Bum;Chang, Su-youne;Jung, Sung Jun
    • The Korean Journal of Physiology and Pharmacology
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    • 제22권5호
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    • pp.547-554
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    • 2018
  • Itching is a common clinical symptom of skin disease that significantly affects a patient's quality of life. Transient receptor potential vanilloid 1 (TRPV1) receptors of keratinocytes and peripheral nerve fibers in skin are involved in the regulation of itching as well as pain. In this study, we investigated whether curcumin, which acts on TRPV1 receptors, affects histamine-induced itching in mice, using behavioral tests and electrophysiological approaches. We found that histamine-induced itching was blocked by topical application of curcumin in a concentration-dependent manner. In ex-vivo recordings, histamine-induced discharges of peripheral nerves were reduced by the application of curcumin, indicating that curcumin acts directly on peripheral nerves. Additionally, curcumin blocked the histamine-induced inward current via activation of TRPV1 (curcumin $IC_{50}=523nM$). However, it did not alter chloroquine-induced itching behavior in mice, which is associated with transient receptor potential ankyrin 1 (TRPA1). Taken together, our results suggest that histamine-induced itching can be blocked by topical application of curcumin through the inhibitory action of curcumin on TRPV1 receptors in peripheral nerves.

An alternative method to reduce anaphylaxis by moxibustion

  • Jeong, Hyun-Ja;Nam, Sun-Young;Lee, Byong-Joo;Kim, Min-Gi;Kim, Jeong-Hwa;Kim, Hyung-Min
    • 셀메드
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    • 제4권2호
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    • pp.12.1-12.12
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    • 2014
  • Epinephrine is a critical drug for patients at risk for anaphylaxis. Here, we suggest moxibustion as an alternative method to reduce anaphylaxis. Moxibustion was applied to the Shimen (CV5) acupoint and found to attenuate compound 48/80-induced mortality. Capsazepine, a transient receptor potential vanilloid (TRPV) 1 antagonist, significantly improved overall survival rates compared to groups treated with moxibustion or 2-aminoethoxydiphenyl borate (an activator of TRPV1, 2, and 3). Probenecid (a TRPV2 agonist) also increased survival rate and reduced histamine levels. Survival rates increased by moxibustion and probenecid were completely inhibited by ruthenium red (a TRPV2 and 3 antagonist) and gadolinium chloride (general TRPV antagonist), respectively. Passive cutaneous anaphylaxis and ear swelling were significantly reduced by moxibustion and probenecid (p < 0.05). In cardiomyocytes, TRPV2 was over-expressed by compound 48/80 and histamine but this increased TRPV2 expression decreased to baseline with moxibustion and probenecid treatment. In addition, intracellular calcium levels increased by compound 48/80 were reduced by probenecid. Overall, these findings suggest that the reduction of anaphylaxis caused by moxibustion could represent a new mechanism of moxibustion related to the regulation of TRPV2 activation and promotion of epinephrine secretion.

흰쥐의 구강악안면 영역에서 포르말린 통증행위반응에 TRPV1 채널의 영향 (Effects of TRPV1 in formalin-induced nociceptive behavior in the orofacial area of rats)

  • 박민경;성미경;이민경
    • 한국산학기술학회논문지
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    • 제15권1호
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    • pp.316-322
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    • 2014
  • 본 연구는 TRPV1 채널의 활성화가 염증성 통증반응 조절에 관여하는지에 관해 조사하였다. 수컷의 Sprague-Dawley계 흰 쥐 (220-260g)을 사용하였으며, 통증행위반응은 약물 주입 후 총 45분간 안면부를 긁거나 문지르는 행위를 지표로 간주하였다. 5% formalin($25{\mu}L$)을 단독투여 한 그룹에서는 유의한 통증행위반응을 관찰할 수 있었으나, capsaicin($0.1{\mu}g$, $1{\mu}g/10{\mu}L$)의 단독 투여한 그룹에서는 통증행위반응의 변화가 나타나지 않았다. 실험동물의 안면부에 TRPV1 채널의 효현제인 capsaicin 을 1시간 전에 주입한 후 동일 부위로 5% formalin 을 투여하게 되면 유의하게 증가된 통증행위반응을 관찰할 수 있었다. 증가된 통증행위반응은 TRPV1의 억제제인 I-RTX의 전처리에 의해 효과적으로 경감되었다(p<0.05). 이상의 결과들은 5% formalin으로 유발된 안면부 염증성 통증행위반응에 TRPV1의 활성화가 통증전도에 영향을 미칠 수 있음을 제시한다.

Discovery of Novel TRPV1 Ligands through Rational Approach Based on Its Putative Endogenous Ligand, 12(S)-HPETE

  • Min, Kyung-Hoon;Lee, Seul;Kim, Hwa-Soon;Suh, Young-Ger
    • Bulletin of the Korean Chemical Society
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    • 제31권6호
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    • pp.1501-1505
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    • 2010
  • We report design and synthesis of the novel TRPV1 ligands through a rational approach. Simplified analogues of 12(S)-HPETE showing TRPV1 agonistic effect are disclosed. Biological evaluation revealed that substitution of functional groups without any change in conformation converted agonist into antagonist. Our work provided key information with regard to TRPV1 agonist/antagonist switching.

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
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    • 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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    • pp.192.2-193
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    • 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)

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Expression of TRP Channels in Mouse Dental Papilla Cell-23 (MDPC-23) Cell Line

  • Shin, Myoung-Sang;Yeon, Kyu-Young;Oh, Seog-Bae;Kim, Joong-Soo
    • International Journal of Oral Biology
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    • 제31권4호
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    • pp.135-140
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    • 2006
  • Temperature signaling can be initiated by members of transient receptor potential (thermo-TRP) channels. Hot and cold substances applied to teeth usually elicit pain sensation. Since odontoblasts constitute a well-defined layer between the pulp and the mineralized dentin, being first to encounter thermal stimulation from oral cavity, they may be involved in sensory transduction process, in addition to their primary function as formation of dentin. We investigated whether thermo-TRP channels are expressed in a odontoblast cell line, MDPC-23. The expressions of thermo-TRP channels were examined using reverse transcription polymerase chain reaction (RT-PCR), immunohistochemistry, fluorometric calcium imaging. Analysis of RT-PCR revealed mRNA expression of TRPV1, TRPV2, TRPV4 and TRPM8, but no TRPV3, TRPA1. Immunohistochemical approach failed to detect TRPV1 expression. Whereas the application of 4-phorbol-12,13-didecanoate($10\;{\mu}M$, a TRPV4 agonist), menthol(1 mM, a TRPM8 agonist) and icilin($10\;{\mu}M$, a TRPM8 agonist) produced the enhancement of intracellular calcium concentration, capsaicin($1\;{\mu}M$, a TRPV1 agonist) did not. Our results suggest that subfamily of thermo-TRP channels expressed in odontoblasts may serve as thermal or mechanical transducer in teeth.

TRPV1 in Salivary Gland Epithelial Cells Is Not Involved in Salivary Secretion via Transcellular Pathway

  • Choi, Seulki;Shin, Yong-Hwan;Namkoong, Eun;Hwang, Sung-Min;Cong, Xin;Yu, Guangyan;Park, Kyungpyo
    • The Korean Journal of Physiology and Pharmacology
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    • 제18권6호
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    • pp.525-530
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    • 2014
  • Transient receptor potential vanilloid subtype 1 (TRPV1) was originally found in sensory neurons. Recently, it has been reported that TRPV1 is expressed in salivary gland epithelial cells (SGEC). However, the physiological role of TRPV1 in salivary secretion remains to be elucidated. We found that TRPV1 is expressed in mouse and human submandibular glands (SMG) and HSG cells, originated from human submandibular gland ducts at both mRNA and protein levels. However, capsaicin (CAP), TRPV1 agonist, had little effect on intracellular free calcium concentration ($[Ca^{2+}]_i$) in these cells, although carbachol consistently increased $[Ca^{2+}]_i$. Exposure of cells to high temperature (> $43^{\circ}C$) or acidic bath solution (pH5.4) did not increase $[Ca^{2+}]_i$, either. We further examined the role of TRPV1 in salivary secretion using TRPV1 knock-out mice. There was no significant difference in the pilocarpine (PILO)-induced salivary flow rate between wild-type and TRPV1 knock-out mice. Saliva flow rate also showed insignificant change in the mice treated with PILO plus CAP compared with that in mice treated with PILO alone. Taken together, our results suggest that although TRPV1 is expressed in SGEC, it appears not to play any direct roles in saliva secretion via transcellular pathway.