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Isopentenyl pyrophosphate is a novel antinociceptive substance that inhibits TRPV3 and TRPA1 ion channels.
Pain. 2011 May; 152(5):1156-1164.PAIN

Abstract

Transient receptor potential ion channels (TRPs) expressed in the periphery sense and electrically transduce noxious stimuli to transmit the signals to the brain. Many natural and synthetic ligands for the sensory TRPs have been found, but little is known about endogenous inhibitors of these TRP channels. Recently, we reported that farnesyl pyrophosphate, an endogenous substance produced in the mevalonate pathway, is a specific activator for TRPV3. Here, we show that isopentenyl pyrophosphate (IPP), an upstream metabolite in the same pathway, is a dual inhibitor for TRPA1 and TRPV3. By using Ca(2+) imaging and voltage clamp experiments with human embryo kidney cell heterologous expression system, cultured sensory neurons, and epidermal keratinocytes, we demonstrate that micromolar IPP suppressed responses to specific agonists of TRPA1 and TRPV3. Consistently, peripheral IPP administration attenuated TRPA1 and TRPV3 agonist-specific acute pain behaviors. Furthermore, local IPP pretreatment significantly reversed mechanical and thermal hypersensitivity of inflamed animals. Taken together, the present study suggests that IPP is a novel endogenous TRPA1 and TRPV3 inhibitor that causes local antinociception. Our results may provide useful chemical information to elucidate TRP physiology in peripheral pain sensation.

Authors+Show Affiliations

Korea University Graduate School of Medicine, Seoul 136-705, Republic of Korea Sensory Research Center, CRI, Seoul National University College of Pharmacy, Seoul 151-742, Republic of Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21353389

Citation

Bang, Sangsu, et al. "Isopentenyl Pyrophosphate Is a Novel Antinociceptive Substance That Inhibits TRPV3 and TRPA1 Ion Channels." Pain, vol. 152, no. 5, 2011, pp. 1156-1164.
Bang S, Yoo S, Yang TJ, et al. Isopentenyl pyrophosphate is a novel antinociceptive substance that inhibits TRPV3 and TRPA1 ion channels. Pain. 2011;152(5):1156-1164.
Bang, S., Yoo, S., Yang, T. J., Cho, H., & Hwang, S. W. (2011). Isopentenyl pyrophosphate is a novel antinociceptive substance that inhibits TRPV3 and TRPA1 ion channels. Pain, 152(5), 1156-1164. https://doi.org/10.1016/j.pain.2011.01.044
Bang S, et al. Isopentenyl Pyrophosphate Is a Novel Antinociceptive Substance That Inhibits TRPV3 and TRPA1 Ion Channels. Pain. 2011;152(5):1156-1164. PubMed PMID: 21353389.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Isopentenyl pyrophosphate is a novel antinociceptive substance that inhibits TRPV3 and TRPA1 ion channels. AU - Bang,Sangsu, AU - Yoo,Sungjae, AU - Yang,Tae-Jin, AU - Cho,Hawon, AU - Hwang,Sun Wook, Y1 - 2011/02/24/ PY - 2010/08/05/received PY - 2010/12/09/revised PY - 2011/01/24/accepted PY - 2011/3/1/entrez PY - 2011/3/1/pubmed PY - 2011/8/24/medline SP - 1156 EP - 1164 JF - Pain JO - Pain VL - 152 IS - 5 N2 - Transient receptor potential ion channels (TRPs) expressed in the periphery sense and electrically transduce noxious stimuli to transmit the signals to the brain. Many natural and synthetic ligands for the sensory TRPs have been found, but little is known about endogenous inhibitors of these TRP channels. Recently, we reported that farnesyl pyrophosphate, an endogenous substance produced in the mevalonate pathway, is a specific activator for TRPV3. Here, we show that isopentenyl pyrophosphate (IPP), an upstream metabolite in the same pathway, is a dual inhibitor for TRPA1 and TRPV3. By using Ca(2+) imaging and voltage clamp experiments with human embryo kidney cell heterologous expression system, cultured sensory neurons, and epidermal keratinocytes, we demonstrate that micromolar IPP suppressed responses to specific agonists of TRPA1 and TRPV3. Consistently, peripheral IPP administration attenuated TRPA1 and TRPV3 agonist-specific acute pain behaviors. Furthermore, local IPP pretreatment significantly reversed mechanical and thermal hypersensitivity of inflamed animals. Taken together, the present study suggests that IPP is a novel endogenous TRPA1 and TRPV3 inhibitor that causes local antinociception. Our results may provide useful chemical information to elucidate TRP physiology in peripheral pain sensation. SN - 1872-6623 UR - https://www.unboundmedicine.com/medline/citation/21353389/Isopentenyl_pyrophosphate_is_a_novel_antinociceptive_substance_that_inhibits_TRPV3_and_TRPA1_ion_channels_ L2 - https://linkinghub.elsevier.com/retrieve/pii/00006396-201105000-00030 DB - PRIME DP - Unbound Medicine ER -