KEGG   PATHWAY: oor04750
Entry
oor04750                    Pathway                                
Name
Inflammatory mediator regulation of TRP channels - Orcinus orca (killer whale)
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
oor04750  Inflammatory mediator regulation of TRP channels
oor04750

Other DBs
GO: 0019233
Organism
Orcinus orca (killer whale) [GN:oor]
Gene
101269181  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X16 [KO:K04515] [EC:2.7.11.17]
101269212  MAPK13; mitogen-activated protein kinase 13 isoform X7 [KO:K04441] [EC:2.7.11.24]
101269458  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
101269805  PLA2G4F; cytosolic phospholipase A2 zeta [KO:K16342] [EC:3.1.1.4]
101269950  IGF1; insulin-like growth factor I isoform X2 [KO:K05459]
101270052  PLA2G4E; cytosolic phospholipase A2 epsilon isoform X1 [KO:K16342] [EC:3.1.1.4]
101270543  PLA2G4A; cytosolic phospholipase A2 isoform X1 [KO:K16342] [EC:3.1.1.4]
101270548  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
101270961  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
101271138  PRKCH; protein kinase C eta type isoform X1 [KO:K18051] [EC:2.7.11.13]
101271639  BDKRB2; B2 bradykinin receptor [KO:K03916]
101271859  HTR2A; 5-hydroxytryptamine receptor 2A [KO:K04157]
101271879  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
101272104  [KO:K07425] [EC:1.14.14.80]
101272289  P2RY2; P2Y purinoceptor 2 [KO:K04269]
101272359  [KO:K07425] [EC:1.14.14.80]
101272376  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
101273023  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
101273078  CALM2; calmodulin-2 [KO:K02183]
101273171  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
101273503  NTRK1; high affinity nerve growth factor receptor isoform X1 [KO:K03176] [EC:2.7.10.1]
101273592  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
101273911  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
101274558  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
101274956  TRPV4; transient receptor potential cation channel subfamily V member 4 [KO:K04973]
101275089  SRC; proto-oncogene tyrosine-protein kinase Src isoform X3 [KO:K05704] [EC:2.7.10.2]
101275243  TRPV1; transient receptor potential cation channel subfamily V member 1 [KO:K05222]
101275504  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
101275666  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 isoform X2 [KO:K04432] [EC:2.7.12.2]
101275670  TRPV3; transient receptor potential cation channel subfamily V member 3 isoform X4 [KO:K04972]
101275696  HRH1; histamine H1 receptor [KO:K04149]
101276350  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
101276402  PRKCE; protein kinase C epsilon type isoform X1 [KO:K18050] [EC:2.7.11.13]
101276418  PRKCG; protein kinase C gamma type isoform X1 [KO:K19663] [EC:2.7.11.13]
101276634  PRKCQ; protein kinase C theta type isoform X2 [KO:K18052] [EC:2.7.11.13]
101277002  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
101277054  TRPM8; transient receptor potential cation channel subfamily M member 8 isoform X1 [KO:K04983]
101277123  PLA2G6; 85/88 kDa calcium-independent phospholipase A2 isoform X3 [KO:K16343] [EC:3.1.1.4]
101277133  BDKRB1; B1 bradykinin receptor [KO:K03915]
101277568  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
101277609  IL1R1; interleukin-1 receptor type 1 isoform X1 [KO:K04386]
101277656  MAPK10; mitogen-activated protein kinase 10 isoform X4 [KO:K04440] [EC:2.7.11.24]
101277874  NGF; beta-nerve growth factor [KO:K02582]
101278075  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
101278368  ADCY1; adenylate cyclase type 1 isoform X1 [KO:K08041] [EC:4.6.1.1]
101278562  F2RL1; proteinase-activated receptor 2 [KO:K04234]
101278649  CALML6; calmodulin-like protein 6 [KO:K02183]
101278974  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X2 [KO:K00922] [EC:2.7.1.153]
101279538  ALOX12; polyunsaturated fatty acid lipoxygenase ALOX12 isoform X3 [KO:K00458] [EC:1.13.11.31]
101279781  [KO:K04634]
101279979  CALM3; calmodulin-3 [KO:K02183]
101280390  [KO:K07413] [EC:1.14.14.1]
101280413  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
101280558  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
101280786  ASIC4; acid-sensing ion channel 4 [KO:K04831]
101280894  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
101281073  [KO:K07413] [EC:1.14.14.1]
101281155  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
101281193  ASIC3; acid-sensing ion channel 3 isoform X3 [KO:K04830]
101281228  MAPK8; mitogen-activated protein kinase 8 isoform X2 [KO:K04440] [EC:2.7.11.24]
101281352  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X2 [KO:K02649]
101281412  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
101281417  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X9 [KO:K05858] [EC:3.1.4.11]
101281498  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X8 [KO:K04515] [EC:2.7.11.17]
101281654  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
101282017  [KO:K02183]
101282504  PTGER2; prostaglandin E2 receptor EP2 subtype [KO:K04259]
101282737  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X2 [KO:K04958]
101282939  [KO:K04632]
101283011  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
101283178  ADCY5; adenylate cyclase type 5 isoform X2 [KO:K08045] [EC:4.6.1.1]
101283651  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
101283768  KNG1; kininogen-1 isoform X1 [KO:K03898]
101283895  [KO:K07425] [EC:1.14.14.80]
101284096  [KO:K02183]
101284509  ASIC1; acid-sensing ion channel 1 isoform X1 [KO:K04829]
101284631  HTR2C; 5-hydroxytryptamine receptor 2C [KO:K04157]
101284892  IL1B; interleukin-1 beta isoform X2 [KO:K04519]
101285216  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
101285437  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
101285541  IL1RAP; interleukin-1 receptor accessory protein isoform X1 [KO:K04723]
101285623  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
101285814  CALM1; calmodulin-1 [KO:K02183]
101286066  HTR2B; 5-hydroxytryptamine receptor 2B [KO:K04157]
101286206  PLA2G4D; cytosolic phospholipase A2 delta isoform X1 [KO:K16342] [EC:3.1.1.4]
101286207  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
101286834  [KO:K04632]
101286983  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
101287513  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X5 [KO:K04515] [EC:2.7.11.17]
101287579  [KO:K04441] [EC:2.7.11.24]
101287701  MAPK9; mitogen-activated protein kinase 9 isoform X5 [KO:K04440] [EC:2.7.11.24]
101287833  [KO:K04441] [EC:2.7.11.24]
101287874  TRPV2; transient receptor potential cation channel subfamily V member 2 isoform X1 [KO:K04971]
101287985  [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
101288108  PTGER4; prostaglandin E2 receptor EP4 subtype [KO:K04261]
101289310  ASIC2; acid-sensing ion channel 2 isoform X1 [KO:K04828]
101289858  ADCY4; adenylate cyclase type 4 isoform X2 [KO:K08044] [EC:4.6.1.1]
105748632  [KO:K02183]
117195357  PLA2G4B; cytosolic phospholipase A2 beta isoform X1 [KO:K16342] [EC:3.1.1.4]
125961823  [KO:K02183]
125961824  [KO:K02183]
125961825  [KO:K02183]
125961826  [KO:K02183]
125961827  [KO:K02183]
125961828  [KO:K02183]
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
Related
pathway
oor00590  Arachidonic acid metabolism
oor04010  MAPK signaling pathway
oor04020  Calcium signaling pathway
KO pathway
ko04750   

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