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Background and Purpose: Transient receptor potential ion channel vanilloid 3 (TRPV3) is expressed in skin keratinocytes and plays an important role in thermal and chemical nociceptions in the periphery. The presence of TRPV3 inhibitors would improve our understanding of TRPV3 function and help to develop receptor-specific analgesics. However, little is known about physiological substances that specifically inhibit TRPV3 activity. Here, we investigated whether 17(R)-resolvin D1 (17R-RvD1), a naturally occurring pro-resolving lipid specifically affects TRPV3 activity.

Experimental Approach: We examined the effect of 17R-RvD1 on sensory TRP channels using Ca(2+) imaging and whole cell electrophysiology experiments in a HEK cell heterologous expression system, cultured sensory neurons and keratinocytes. We also examined changes in sensory TRP agonist-specific acute licking/flicking or flinching behaviours and mechanical and thermal pain behaviours using Hargreaves, Randall-Selitto and von Frey assay systems in the absence and presence of inflammation.

Key Results: We showed that 17R-RvD1 specifically suppresses TRPV3-mediated activity at nanomolar and micromolar concentrations. The voltage-dependence of TRPV3 activation by camphor was shifted rightwards by 17R-RvD1, which indicates its inhibitory mechanism is as a result of a shift in voltage-dependence. Consistently, TRPV3-specific acute pain behaviours were attenuated by locally injected 17R-RvD1. Moreover, the administration of 17R-RvD1 significantly reversed the thermal hypersensitivity that occurs during an inflammatory response. Knockdown of epidermal TRPV3 blunted these antinociceptive effects of 17R-RvD1.

Conclusions and Implications: 17R-RvD1 is a novel natural inhibitory substance specific for TRPV3. The results of our behavioural studies suggest that 17R-RvD1 has acute analgesic potential via TRPV3-specific mechanisms.

Titel:	17(R)-resolvin D1 specifically inhibits transient receptor potential ion channel vanilloid 3 leading to peripheral antinociception.
Autor/in / Beteiligte Person:	Bang, S ; Yoo, S ; Yang, TJ ; Cho, H ; Hwang, SW
Link:	Full Text Finder (Volltext)
Zeitschrift:	British journal of pharmacology, Jg. 165 (2012-02-01), Heft 3, S. 683-92
Veröffentlichung:	London : Wiley ; <i>Original Publication</i>: London, Macmillian Journals Ltd., 2012
Medientyp:	academicJournal
ISSN:	1476-5381 (electronic)
DOI:	10.1111/j.1476-5381.2011.01568.x
Schlagwort:	Analgesics pharmacology Animals Anti-Inflammatory Agents pharmacology Capsaicin Carrageenan Cell Line Docosahexaenoic Acids pharmacology Freund's Adjuvant Ganglia, Spinal cytology HEK293 Cells Hot Temperature Humans Inflammation chemically induced Inflammation drug therapy Inflammation physiopathology Keratinocytes drug effects Keratinocytes physiology Male Mice Mice, Inbred ICR Mice, Knockout Pain chemically induced Pain physiopathology Rats Rats, Sprague-Dawley Sensory Receptor Cells drug effects Sensory Receptor Cells physiology TRPV Cation Channels deficiency TRPV Cation Channels genetics TRPV Cation Channels physiology Analgesics therapeutic use Anti-Inflammatory Agents therapeutic use Docosahexaenoic Acids therapeutic use Pain drug therapy TRPV Cation Channels antagonists & inhibitors
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, Non-U.S. Gov't Language: English [Br J Pharmacol] 2012 Feb; Vol. 165 (3), pp. 683-92. MeSH Terms: Analgesics / therapeutic use ; Anti-Inflammatory Agents / therapeutic use ; Docosahexaenoic Acids / therapeutic use ; Pain / drug therapy ; TRPV Cation Channels / *antagonists & inhibitors ; Analgesics / pharmacology ; Animals ; Anti-Inflammatory Agents / pharmacology ; Capsaicin ; Carrageenan ; Cell Line ; Docosahexaenoic Acids / pharmacology ; Freund's Adjuvant ; Ganglia, Spinal / cytology ; HEK293 Cells ; Hot Temperature ; Humans ; Inflammation / chemically induced ; Inflammation / drug therapy ; Inflammation / physiopathology ; Keratinocytes / drug effects ; Keratinocytes / physiology ; Male ; Mice ; Mice, Inbred ICR ; Mice, Knockout ; Pain / chemically induced ; Pain / physiopathology ; Rats ; Rats, Sprague-Dawley ; Sensory Receptor Cells / drug effects ; Sensory Receptor Cells / physiology ; TRPV Cation Channels / deficiency ; TRPV Cation Channels / genetics ; TRPV Cation Channels / physiology References: J Dent Res. 2010 Dec;89(12):1455-60. (PMID: 20935279) ; Br J Pharmacol. 2011 Nov;164 Suppl 1:S1-324. (PMID: 22040146) ; J Neurosci. 2008 Dec 17;28(51):13727-37. (PMID: 19091963) ; Br J Pharmacol. 2007 Jun;151(4):530-40. (PMID: 17420775) ; Arch Pharm Res. 2010 Oct;33(10):1509-20. (PMID: 21052930) ; Science. 2002 Jun 14;296(5575):2046-9. (PMID: 12016205) ; Br J Pharmacol. 2010 Oct;161(3):707-20. (PMID: 20880407) ; Pain. 2011 May;152(5):1156-1164. (PMID: 21353389) ; J Pharmacol Exp Ther. 2008 Aug;326(2):432-42. (PMID: 18499743) ; Nature. 2003 Jul 24;424(6947):434-8. (PMID: 12879072) ; Cell. 2003 Mar 21;112(6):819-29. (PMID: 12654248) ; Proc Natl Acad Sci U S A. 2002 Jul 23;99(15):10150-5. (PMID: 12097645) ; J Clin Invest. 2010 Apr;120(4):1240-52. (PMID: 20335661) ; Mol Pharmacol. 2008 Feb;73(2):274-81. (PMID: 18000030) ; Nat Rev Drug Discov. 2009 Jan;8(1):55-68. (PMID: 19116627) ; Proc Natl Acad Sci U S A. 2009 Nov 3;106(44):18820-4. (PMID: 19843694) ; J Neurosci. 2004 Apr 7;24(14):3663-71. (PMID: 15071115) ; Biochem Biophys Res Commun. 2008 May 30;370(2):295-300. (PMID: 18371303) ; Mol Pharmacol. 2009 Jun;75(6):1262-79. (PMID: 19297520) ; Neurosci Lett. 2007 Sep 25;425(2):120-5. (PMID: 17850966) ; J Biol Chem. 2010 Jun 18;285(25):19362-71. (PMID: 20395302) ; J Cell Physiol. 2006 Jul;208(1):201-12. (PMID: 16557504) ; Proc Natl Acad Sci U S A. 2010 Jan 26;107(4):1660-5. (PMID: 20080636) ; J Neurosci. 2008 Mar 5;28(10):2485-94. (PMID: 18322093) ; Proc Natl Acad Sci U S A. 2009 Feb 3;106(5):1626-31. (PMID: 19164517) ; Neuron. 2004 Mar 25;41(6):849-57. (PMID: 15046718) ; Mol Pain. 2007 Dec 17;3:40. (PMID: 18086313) ; J Neurosci. 2001 Oct 1;21(19):7463-73. (PMID: 11567036) ; J Physiol. 2007 Feb 1;578(Pt 3):715-33. (PMID: 17124270) ; Br J Pharmacol. 2011 Sep;164(2):278-93. (PMID: 21418187) ; Neuron. 1998 Sep;21(3):531-43. (PMID: 9768840) ; Pharmacol Rev. 1993 Sep;45(3):309-79. (PMID: 8248282) ; Science. 2005 Mar 4;307(5714):1468-72. (PMID: 15746429) ; Nature. 2001 Jun 21;411(6840):957-62. (PMID: 11418861) ; Eur J Neurosci. 2007 Nov;26(9):2516-23. (PMID: 17970723) ; Trends Immunol. 2007 Apr;28(4):176-83. (PMID: 17337246) ; J Biol Chem. 2007 Mar 30;282(13):9323-9334. (PMID: 17244615) ; J Exp Med. 2002 Oct 21;196(8):1025-37. (PMID: 12391014) ; Nat Med. 2010 May;16(5):592-7, 1p following 597. (PMID: 20383154) ; Pflugers Arch. 2009 Oct;458(6):1093-102. (PMID: 19669158) ; Nat Immunol. 2001 Jul;2(7):612-9. (PMID: 11429545) ; Nature. 2002 Mar 7;416(6876):52-8. (PMID: 11882888) ; Biochem Biophys Res Commun. 2009 Nov 20;389(3):490-4. (PMID: 19737537) ; Proc Natl Acad Sci U S A. 2000 May 23;97(11):6155-60. (PMID: 10823958) Substance Nomenclature: 0 (Analgesics) ; 0 (Anti-Inflammatory Agents) ; 0 (TRPV Cation Channels) ; 0 (TRPV1 protein, mouse) ; 0 (TRPV3 protein, human) ; 0 (Trpv3 protein, mouse) ; 0 (resolvin D1) ; 25167-62-8 (Docosahexaenoic Acids) ; 9000-07-1 (Carrageenan) ; 9007-81-2 (Freund's Adjuvant) ; S07O44R1ZM (Capsaicin) Entry Date(s): Date Created: 20110702 Date Completed: 20120508 Latest Revision: 20211020 Update Code: 20231215 PubMed Central ID: PMC3315040

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17(R)-resolvin D1 specifically inhibits transient receptor potential ion channel vanilloid 3 leading to peripheral antinociception.