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Farnesyl pyrophosphate is a novel pain-producing molecule via specific activation of TRPV3.
J Biol Chem. 2010 Jun 18; 285(25):19362-71.JB

Abstract

Temperature-sensitive transient receptor potential ion channels (thermoTRPs) expressed in epidermal keratinocytes and sensory afferents play an important role as peripheral pain detectors for our body. Many natural and synthetic compounds have been found to act on the thermoTRPs leading to altered nociception, but little is known about endogenous painful molecules activating TRPV3. Here, we show that farnesyl pyrophosphate (FPP), an intermediate metabolite in the mevalonate pathway, specifically activates TRPV3 among six thermoTRPs using Ca(2+) imaging and electrophysiology with cultured keratinocytes and TRPV3-overexpressing cells. Agonistic potencies of related compounds in the FPP metabolism were ignorable. Voltage-dependence of TRPV3 was shifted by FPP, which appears to be the activation mechanism. An intraplantar injection of FPP acutely elicits nociceptive behaviors in inflamed animals, indicating that FPP is a novel endogenous pain-producing substance via TRPV3 activation. Co-culture experiments demonstrated that this FPP-evoked signal in the keratinocytes is transmitted to sensory neurons. In addition, FPP reduced TRPV3 heat threshold resulting in heightened behavioral sensitivity to noxious heat. Taken together, our data suggest that FPP is the firstly identified endogenous TRPV3 activator that causes nociception. Our results may provide useful chemical information to elucidate TRPV3 physiology and novel pain-related metabolisms.

Authors+Show Affiliations

Korea University Graduate School of Medicine, Seoul 136-705, 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

20395302

Citation

Bang, Sangsu, et al. "Farnesyl Pyrophosphate Is a Novel Pain-producing Molecule Via Specific Activation of TRPV3." The Journal of Biological Chemistry, vol. 285, no. 25, 2010, pp. 19362-71.
Bang S, Yoo S, Yang TJ, et al. Farnesyl pyrophosphate is a novel pain-producing molecule via specific activation of TRPV3. J Biol Chem. 2010;285(25):19362-71.
Bang, S., Yoo, S., Yang, T. J., Cho, H., & Hwang, S. W. (2010). Farnesyl pyrophosphate is a novel pain-producing molecule via specific activation of TRPV3. The Journal of Biological Chemistry, 285(25), 19362-71. https://doi.org/10.1074/jbc.M109.087742
Bang S, et al. Farnesyl Pyrophosphate Is a Novel Pain-producing Molecule Via Specific Activation of TRPV3. J Biol Chem. 2010 Jun 18;285(25):19362-71. PubMed PMID: 20395302.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Farnesyl pyrophosphate is a novel pain-producing molecule via specific activation of TRPV3. AU - Bang,Sangsu, AU - Yoo,Sungjae, AU - Yang,Tae-Jin, AU - Cho,Hawon, AU - Hwang,Sun Wook, Y1 - 2010/04/15/ PY - 2010/4/17/entrez PY - 2010/4/17/pubmed PY - 2010/7/22/medline SP - 19362 EP - 71 JF - The Journal of biological chemistry JO - J Biol Chem VL - 285 IS - 25 N2 - Temperature-sensitive transient receptor potential ion channels (thermoTRPs) expressed in epidermal keratinocytes and sensory afferents play an important role as peripheral pain detectors for our body. Many natural and synthetic compounds have been found to act on the thermoTRPs leading to altered nociception, but little is known about endogenous painful molecules activating TRPV3. Here, we show that farnesyl pyrophosphate (FPP), an intermediate metabolite in the mevalonate pathway, specifically activates TRPV3 among six thermoTRPs using Ca(2+) imaging and electrophysiology with cultured keratinocytes and TRPV3-overexpressing cells. Agonistic potencies of related compounds in the FPP metabolism were ignorable. Voltage-dependence of TRPV3 was shifted by FPP, which appears to be the activation mechanism. An intraplantar injection of FPP acutely elicits nociceptive behaviors in inflamed animals, indicating that FPP is a novel endogenous pain-producing substance via TRPV3 activation. Co-culture experiments demonstrated that this FPP-evoked signal in the keratinocytes is transmitted to sensory neurons. In addition, FPP reduced TRPV3 heat threshold resulting in heightened behavioral sensitivity to noxious heat. Taken together, our data suggest that FPP is the firstly identified endogenous TRPV3 activator that causes nociception. Our results may provide useful chemical information to elucidate TRPV3 physiology and novel pain-related metabolisms. SN - 1083-351X UR - https://www.unboundmedicine.com/medline/citation/20395302/Farnesyl_pyrophosphate_is_a_novel_pain_producing_molecule_via_specific_activation_of_TRPV3_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0021-9258(20)58069-1 DB - PRIME DP - Unbound Medicine ER -