Cutaneous Nociception Evoked by 15-delta PGJ2 Via Activation of Ion Channel TRPA1

Overview

Journal Mol Pain

Date 2008 Aug 2

PMID 18671867

Citations 63

Authors

Lillian Cruz-Orengo

Ajay Dhaka

Robert J Heuermann

Timothy J Young

Michael C Montana

Eric J Cavanaugh

Donghee Kim

Gina M Story

Affiliations

Soon will be listed here.

Abstract

Background: A number of prostaglandins (PGs) sensitize dorsal root ganglion (DRG) neurons and contribute to inflammatory hyperalgesia by signaling through specific G protein-coupled receptors (GPCRs). One mechanism whereby PGs sensitize these neurons is through modulation of "thermoTRPs," a subset of ion channels activated by temperature belonging to the Transient Receptor Potential ion channel superfamily. Acrid, electrophilic chemicals including cinnamaldehyde (CA) and allyl isothiocyanate (AITC), derivatives of cinnamon and mustard oil respectively, activate thermoTRP member TRPA1 via direct modification of channel cysteine residues.

Results: Our search for endogenous chemical activators utilizing a bioactive lipid library screen identified a cyclopentane PGD2 metabolite, 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2), as a TRPA1 agonist. Similar to CA and AITC, this electrophilic molecule is known to modify cysteines of cellular target proteins. Electophysiological recordings verified that 15d-PGJ2 specifically activates TRPA1 and not TRPV1 or TRPM8 (thermoTRPs also enriched in DRG). Accordingly, we identified a population of mouse DRG neurons responsive to 15d-PGJ2 and AITC that is absent in cultures derived from TRPA1 knockout mice. The irritant molecules that activate TRPA1 evoke nociceptive responses. However, 15d-PGJ2 has not been correlated with painful sensations; rather, it is considered to mediate anti-inflammatory processes via binding to the nuclear peroxisome proliferator-activated receptor gamma (PPARgamma). Our in vivo studies revealed that 15d-PGJ2 induced acute nociceptive responses when administered cutaneously. Moreover, mice deficient in the TRPA1 channel failed to exhibit such behaviors.

Conclusion: In conclusion, we show that 15d-PGJ2 induces acute nociception when administered cutaneously and does so via a TRPA1-specific mechanism.

Citing Articles

Inhibitory effects of linalool, an essential oil component of , on nociceptive TRPA1 and voltage-gated Ca channels in mouse sensory neurons.

Hashimoto M, Takahashi K, Ohta T Biochem Biophys Rep. 2023; 34:101468.

PMID: 37102121 PMC: 10123348. DOI: 10.1016/j.bbrep.2023.101468.

Endogenous Derivatives of Linoleic Acid and their Stable Analogs Are Potential Pain Mediators.

Wheeler J, Domenichiello A, Jensen J, Keyes G, Maiden K, Davis J JID Innov. 2023; 3(2):100177.

PMID: 36876220 PMC: 9982331. DOI: 10.1016/j.xjidi.2022.100177.

TRPA1 Role in Inflammatory Disorders: What Is Known So Far?.

Landini L, Souza Monteiro de Araujo D, Titiz M, Geppetti P, Nassini R, De Logu F Int J Mol Sci. 2022; 23(9).

PMID: 35562920 PMC: 9101260. DOI: 10.3390/ijms23094529.

Strain and sex differences in somatosensation and sociability during experimental autoimmune encephalomyelitis.

Ondek K, Nasirishargh A, Dayton J, Nuno M, Cruz-Orengo L Brain Behav Immun Health. 2021; 14:100262.

PMID: 34589768 PMC: 8474462. DOI: 10.1016/j.bbih.2021.100262.

The TRPA1 Agonist Cinnamaldehyde Induces the Secretion of HCO by the Porcine Colon.

Manneck D, Manz G, Braun H, Rosendahl J, Stumpff F Int J Mol Sci. 2021; 22(10).

PMID: 34068986 PMC: 8156935. DOI: 10.3390/ijms22105198.

References

Bautista D, Jordt S, Nikai T, Tsuruda P, Read A, Poblete J . TRPA1 mediates the inflammatory actions of environmental irritants and proalgesic agents. Cell. 2006; 124(6):1269-82. DOI: 10.1016/j.cell.2006.02.023. View

Story G, Peier A, Reeve A, Eid S, Mosbacher J, Hricik T . ANKTM1, a TRP-like channel expressed in nociceptive neurons, is activated by cold temperatures. Cell. 2003; 112(6):819-29. DOI: 10.1016/s0092-8674(03)00158-2. View

Taylor-Clark T, Undem B, Macglashan Jr D, Ghatta S, Carr M, McAlexander M . Prostaglandin-induced activation of nociceptive neurons via direct interaction with transient receptor potential A1 (TRPA1). Mol Pharmacol. 2007; 73(2):274-81. DOI: 10.1124/mol.107.040832. View

Macpherson L, Geierstanger B, Viswanath V, Bandell M, Eid S, Hwang S . The pungency of garlic: activation of TRPA1 and TRPV1 in response to allicin. Curr Biol. 2005; 15(10):929-34. DOI: 10.1016/j.cub.2005.04.018. View

Kliewer S, Lenhard J, Willson T, Patel I, Morris D, Lehmann J . A prostaglandin J2 metabolite binds peroxisome proliferator-activated receptor gamma and promotes adipocyte differentiation. Cell. 1995; 83(5):813-9. DOI: 10.1016/0092-8674(95)90194-9. View

Gilroy D, Colville-Nash P, Willis D, Chivers J, Paul-Clark M, Willoughby D . Inducible cyclooxygenase may have anti-inflammatory properties. Nat Med. 1999; 5(6):698-701. DOI: 10.1038/9550. View

Andersson D, Gentry C, Moss S, Bevan S . Transient receptor potential A1 is a sensory receptor for multiple products of oxidative stress. J Neurosci. 2008; 28(10):2485-94. PMC: 2709206. DOI: 10.1523/JNEUROSCI.5369-07.2008. View

Hinman A, Chuang H, Bautista D, Julius D . TRP channel activation by reversible covalent modification. Proc Natl Acad Sci U S A. 2006; 103(51):19564-8. PMC: 1748265. DOI: 10.1073/pnas.0609598103. View

Ricote M, Li A, Willson T, Kelly C, Glass C . The peroxisome proliferator-activated receptor-gamma is a negative regulator of macrophage activation. Nature. 1998; 391(6662):79-82. DOI: 10.1038/34178. View

10.

Shibata T, Kondo M, Osawa T, Shibata N, Kobayashi M, Uchida K . 15-deoxy-delta 12,14-prostaglandin J2. A prostaglandin D2 metabolite generated during inflammatory processes. J Biol Chem. 2002; 277(12):10459-66. DOI: 10.1074/jbc.M110314200. View

11.

Dhaka A, Viswanath V, Patapoutian A . Trp ion channels and temperature sensation. Annu Rev Neurosci. 2006; 29:135-61. DOI: 10.1146/annurev.neuro.29.051605.112958. View

12.

Kim D, Cavanaugh E . Requirement of a soluble intracellular factor for activation of transient receptor potential A1 by pungent chemicals: role of inorganic polyphosphates. J Neurosci. 2007; 27(24):6500-9. PMC: 6672444. DOI: 10.1523/JNEUROSCI.0623-07.2007. View

13.

Straus D, Pascual G, Li M, Welch J, Ricote M, Hsiang C . 15-deoxy-delta 12,14-prostaglandin J2 inhibits multiple steps in the NF-kappa B signaling pathway. Proc Natl Acad Sci U S A. 2000; 97(9):4844-9. PMC: 18320. DOI: 10.1073/pnas.97.9.4844. View

14.

Scher J, Pillinger M . 15d-PGJ2: the anti-inflammatory prostaglandin?. Clin Immunol. 2005; 114(2):100-9. DOI: 10.1016/j.clim.2004.09.008. View

15.

Soares A, Nosjean O, Cozzone D, DOrazio D, Becchi M, Guichardant M . Covalent binding of 15-deoxy-delta12,14-prostaglandin J2 to PPARgamma. Biochem Biophys Res Commun. 2005; 337(2):521-5. DOI: 10.1016/j.bbrc.2005.09.085. View

16.

Bandell M, Story G, Hwang S, Viswanath V, Eid S, Petrus M . Noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin. Neuron. 2004; 41(6):849-57. DOI: 10.1016/s0896-6273(04)00150-3. View

17.

Kwan K, Allchorne A, Vollrath M, Christensen A, Zhang D, Woolf C . TRPA1 contributes to cold, mechanical, and chemical nociception but is not essential for hair-cell transduction. Neuron. 2006; 50(2):277-89. DOI: 10.1016/j.neuron.2006.03.042. View

18.

Jiang C, Ting A, Seed B . PPAR-gamma agonists inhibit production of monocyte inflammatory cytokines. Nature. 1998; 391(6662):82-6. DOI: 10.1038/34184. View

19.

Jordt S, Bautista D, Chuang H, McKemy D, Zygmunt P, Hogestatt E . Mustard oils and cannabinoids excite sensory nerve fibres through the TRP channel ANKTM1. Nature. 2004; 427(6971):260-5. DOI: 10.1038/nature02282. View

20.

Macpherson L, Xiao B, Kwan K, Petrus M, Dubin A, Hwang S . An ion channel essential for sensing chemical damage. J Neurosci. 2007; 27(42):11412-5. PMC: 6673017. DOI: 10.1523/JNEUROSCI.3600-07.2007. View