KEGG PATHWAY: ko04750

PATHWAY: ko04750

Entry

ko04750                     Pathway

Name

Inflammatory mediator regulation of TRP channels

Description

The TRP channels that exhibit a unique response to temperature have been given the name thermo-TRPs. Among all thermo- TRP channels, TRPV1-4, TRPM8, and TRPA1 are expressed in subsets of nociceptive dorsal root ganglion (DRG) neuron cell bodies including their peripheral and central projections. These channels can be modulated indirectly by inflammatory mediators such as PGE2, bradykinin, ATP, NGF, and proinflammatory cytokines that are generated during tissue injury. While the noxious heat receptor TRPV1 is sensitized (that is, their excitability can be increased) by post-translational modifications upon activation of G-protein coupled receptors (GPCRs) or tyrosine kinase receptors, the receptors for inflammatory mediators, the same action appears to mainly desensitize TRPM8, the main somatic innocuous cold sensor. This aforementioned sensitization could allow the receptor to become active at body temperature, so it not only contributes toward thermal hypersensitivity but also is possibly a substrate for ongoing persistent pain.

Class

Organismal Systems; Sensory system

Pathway map

ko04750

Inflammatory mediator regulation of TRP channels

Drug

D02818

Allyl isothiocyanate (USP)

Other DBs

GO:

0019233

Orthology

K00458

ALOX12; arachidonate 12-lipoxygenase [EC:1.13.11.31]

K00922

PIK3CA_B_D; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153]

K01116

PLCG1; phosphatidylinositol phospholipase C, gamma-1 [EC:3.1.4.11]

K02183

CALM; calmodulin

K02582

NGFB; nerve growth factor, beta

K02649

PIK3R1_2_3; phosphoinositide-3-kinase regulatory subunit alpha/beta/delta

K02677

PRKCA; classical protein kinase C alpha type [EC:2.7.11.13]

K03176

NTRK1, TRKA; neurotrophic tyrosine kinase receptor type 1 [EC:2.7.10.1]

K03898

KNG, BK; kininogen

K03915

BDKRB1; bradykinin receptor B1

K03916

BDKRB2; bradykinin receptor B2

K04149

HRH1; histamine receptor H1

K04157

HTR2; 5-hydroxytryptamine receptor 2

K04234

F2RL1, PAR2; coagulation factor II (thrombin) receptor-like 1

K04259

PTGER2; prostaglandin E receptor 2

K04261

PTGER4; prostaglandin E receptor 4

K04269

P2RY2; P2Y purinoceptor 2

K04345

PKA; protein kinase A [EC:2.7.11.11]

K04386

IL1R1, CD121a; interleukin 1 receptor type I

K04432

MAP2K3, MKK3; mitogen-activated protein kinase kinase 3 [EC:2.7.12.2]

K04433

MAP2K6, MKK6; mitogen-activated protein kinase kinase 6 [EC:2.7.12.2]

K04440

JNK; mitogen-activated protein kinase 8/9/10 (c-Jun N-terminal kinase) [EC:2.7.11.24]

K04441

P38; p38 MAP kinase [EC:2.7.11.24]

K04515

CAMK2; calcium/calmodulin-dependent protein kinase (CaM kinase) II [EC:2.7.11.17]

K04519

IL1B; interleukin 1 beta

K04632

GNAS; guanine nucleotide-binding protein G(s) subunit alpha

K04634

GNAQ; guanine nucleotide-binding protein G(q) subunit alpha

K04723

IL1RAP; interleukin 1 receptor accessory protein

K04828

ASIC2, ACCN1, BNAC1; acid-sensing ion channel 2

K04829

ASIC1, ACCN2, BNAC2; acid-sensing ion channel 1

K04830

ASIC3, ACCN3; acid-sensing ion channel 3

K04831

ASIC4, ACCN4, BNAC4; acid-sensing ion channel 4

K04832

ASIC5, ACCN5; acid-sensing ion channel 5

K04958

ITPR1; inositol 1,4,5-triphosphate receptor type 1

K04959

ITPR2; inositol 1,4,5-triphosphate receptor type 2

K04960

ITPR3; inositol 1,4,5-triphosphate receptor type 3

K04971

TRPV2; transient receptor potential cation channel subfamily V member 2

K04972

TRPV3; transient receptor potential cation channel subfamily V member 3

K04973

TRPV4; transient receptor potential cation channel subfamily V member 4

K04983

TRPM8; transient receptor potential cation channel subfamily M member 8

K04984

TRPA1, ANKTM1; transient receptor potential cation channel subfamily A member 1

K05222

TRPV1; transient receptor potential cation channel subfamily V member 1

K05451

NGFA; nerve growth factor, alpha

K05459

IGF1; insulin-like growth factor 1

K05704

SRC; tyrosine-protein kinase Src [EC:2.7.10.2]

K05858

PLCB; phosphatidylinositol phospholipase C, beta [EC:3.1.4.11]

K05859

PLCG2; phosphatidylinositol phospholipase C, gamma-2 [EC:3.1.4.11]

K06068

PRKCD; novel protein kinase C delta type [EC:2.7.11.13]

K06269

PPP1C; serine/threonine-protein phosphatase PP1 catalytic subunit [EC:3.1.3.16]

K07413

CYP2C; cytochrome P450 family 2 subfamily C [EC:1.14.14.1]

K07418

CYP2J; cytochrome P450 family 2 subfamily J [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]

K07425

CYP4A; long-chain fatty acid omega-monooxygenase [EC:1.14.14.80]

K08041

ADCY1; adenylate cyclase 1 [EC:4.6.1.1]

K08042

ADCY2; adenylate cyclase 2 [EC:4.6.1.1]

K08043

ADCY3; adenylate cyclase 3 [EC:4.6.1.1]

K08044

ADCY4; adenylate cyclase 4 [EC:4.6.1.1]

K08045

ADCY5; adenylate cyclase 5 [EC:4.6.1.1]

K08046

ADCY6; adenylate cyclase 6 [EC:4.6.1.1]

K08047

ADCY7; adenylate cyclase 7 [EC:4.6.1.1]

K08048

ADCY8; adenylate cyclase 8 [EC:4.6.1.1]

K08049

ADCY9; adenylate cyclase 9 [EC:4.6.1.1]

K16342

PLA2G4, CPLA2; cytosolic phospholipase A2 [EC:3.1.1.4]

K16343

PLA2G6, IPLA2; calcium-independent phospholipase A2 [EC:3.1.1.4]

K18050

PRKCE; novel protein kinase C epsilon type [EC:2.7.11.13]

K18051

PRKCH; novel protein kinase C eta type [EC:2.7.11.13]

K18052

PRKCQ; novel protein kinase C theta type [EC:2.7.11.13]

K19662

PRKCB; classical protein kinase C beta type [EC:2.7.11.13]

K19663

PRKCG; classical protein kinase C gamma type [EC:2.7.11.13]

Compound

C00002

ATP

C00076

Calcium cation

C00080

H+

C00165

Diacylglycerol

C00219

Arachidonate

C00388

Histamine

C00400

(-)-Menthol

C00469

Ethanol

C00575

3',5'-Cyclic AMP

C00584

Prostaglandin E2

C00780

Serotonin

C00808

(+)-Camphor

C00809

(-)-Camphor

C00903

Cinnamaldehyde

C01245

D-myo-Inositol 1,4,5-trisphosphate

C01330

Sodium cation

C02165

Leukotriene B4

C04742

(15S)-15-Hydroxy-5,8,11-cis-13-trans-eicosatetraenoate

C04805

5(S)-HETE

C05965

12(S)-HPETE

C05966

15(S)-HPETE

C06254

Lysophospholipid

C06866

Capsaicin

C07600

Allicin

C09155

Phorbol

C09179

Resiniferatoxin

C09844

1,8-Cineole

C11695

Anandamide

C12083

(5Z,7E,9E,14Z,17Z)-Icosapentaenoate

C12271

N-Arachidonyldopamine

C14768

5,6-EET

C14769

8,9-EET

C19317

Allyl isothiocyanate

C20171

Icilin

C20698

2-Aminoethyl diphenylborinate

Reference

PMID:15820689

Authors

Wang H, Woolf CJ

Title

Pain TRPs.

Journal

Neuron 46:9-12 (2005)
DOI:10.1016/j.neuron.2005.03.011

Reference

PMID:17321113

Authors

Levine JD, Alessandri-Haber N

Title

TRP channels: targets for the relief of pain.

Journal

Biochim Biophys Acta 1772:989-1003 (2007)
DOI:10.1016/j.bbadis.2007.01.008

Reference

PMID:18427980

Authors

Cheng JK, Ji RR

Title

Intracellular signaling in primary sensory neurons and persistent pain.

Journal

Neurochem Res 33:1970-8 (2008)
DOI:10.1007/s11064-008-9711-z

Reference

PMID:24099085

Authors

Julius D

Title

TRP channels and pain.

Journal

Annu Rev Cell Dev Biol 29:355-84 (2013)
DOI:10.1146/annurev-cellbio-101011-155833

Reference

PMID:12838328

Authors

Patapoutian A, Peier AM, Story GM, Viswanath V

Title

ThermoTRP channels and beyond: mechanisms of temperature sensation.

Journal

Nat Rev Neurosci 4:529-39 (2003)
DOI:10.1038/nrn1141

Reference

PMID:16776582

Authors

Dhaka A, Viswanath V, Patapoutian A

Title

Trp ion channels and temperature sensation.

Journal

Annu Rev Neurosci 29:135-61 (2006)
DOI:10.1146/annurev.neuro.29.051605.112958

Reference

PMID:18615141

Authors

Story GM

Title

The emerging role of TRP channels in mechanisms of temperature and pain sensation.

Journal

Curr Neuropharmacol 4:183-96 (2006)
DOI:10.2174/157015906778019482

Reference

PMID:17548207

Authors

Velazquez KT, Mohammad H, Sweitzer SM

Title

Protein kinase C in pain: involvement of multiple isoforms.

Journal

Pharmacol Res 55:578-89 (2007)
DOI:10.1016/j.phrs.2007.04.006

Reference

PMID:16319926

Authors

Zhang X, Huang J, McNaughton PA

Title

NGF rapidly increases membrane expression of TRPV1 heat-gated ion channels.

Journal

EMBO J 24:4211-23 (2005)
DOI:10.1038/sj.emboj.7600893

Reference

PMID:19074743

Authors

Bessac BF, Jordt SE

Title

Breathtaking TRP channels: TRPA1 and TRPV1 in airway chemosensation and reflex control.

Journal

Physiology (Bethesda) 23:360-70 (2008)
DOI:10.1152/physiol.00026.2008

Reference

PMID:17684094

Authors

Trevisani M, Siemens J, Materazzi S, Bautista DM, Nassini R, Campi B, Imamachi N, Andre E, Patacchini R, Cottrell GS, Gatti R, Basbaum AI, Bunnett NW, Julius D, Geppetti P

Title

4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1.

Journal

Proc Natl Acad Sci U S A 104:13519-24 (2007)
DOI:10.1073/pnas.0705923104

Reference

PMID:21841075

Authors

Latorre R, Brauchi S, Madrid R, Orio P

Title

A cool channel in cold transduction.

Journal

Physiology (Bethesda) 26:273-85 (2011)
DOI:10.1152/physiol.00004.2011

Reference

PMID:20932256

Authors

Babes A, Ciobanu AC, Neacsu C, Babes RM

Title

TRPM8, a sensor for mild cooling in mammalian sensory nerve endings.

Journal

Curr Pharm Biotechnol 12:78-88 (2011)
DOI:10.2174/138920111793937835

Reference

PMID:23000387

Authors

Loyd DR, Henry MA, Hargreaves KM

Title

Serotonergic neuromodulation of peripheral nociceptors.

Journal

Semin Cell Dev Biol 24:51-7 (2013)
DOI:10.1016/j.semcdb.2012.09.002

Reference

PMID:17124270

Authors

Grant AD, Cottrell GS, Amadesi S, Trevisani M, Nicoletti P, Materazzi S, Altier C, Cenac N, Zamponi GW, Bautista-Cruz F, Lopez CB, Joseph EK, Levine JD, Liedtke W, Vanner S, Vergnolle N, Geppetti P, Bunnett NW

Title

Protease-activated receptor 2 sensitizes the transient receptor potential vanilloid 4 ion channel to cause mechanical hyperalgesia in mice.

Journal

J Physiol 578:715-33 (2007)
DOI:10.1113/jphysiol.2006.121111

Reference

PMID:22470230

Authors

Mandadi S, Armati PJ, Roufogalis BD

Title

Protein kinase C modulation of thermo-sensitive transient receptor potential channels: Implications for pain signaling.

Journal

J Nat Sci Biol Med 2:13-25 (2011)
DOI:10.4103/0976-9668.82311