KEGG   PATHWAY: sara04750
Entry
sara04750                   Pathway                                
Name
Inflammatory mediator regulation of TRP channels - Sorex araneus (European shrew)
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
sara04750  Inflammatory mediator regulation of TRP channels
sara04750

Other DBs
GO: 0019233
Organism
Sorex araneus (European shrew) [GN:sara]
Gene
101536910  [KO:K06269] [EC:3.1.3.16]
101536977  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
101537237  IL1R1; interleukin-1 receptor type 1 [KO:K04386]
101537598  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
101537807  TRPV1; transient receptor potential cation channel subfamily V member 1 [KO:K05222]
101538073  TRPV3; transient receptor potential cation channel subfamily V member 3 isoform X1 [KO:K04972]
101538553  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
101538594  [KO:K07413] [EC:1.14.14.1]
101538700  [KO:K06269] [EC:3.1.3.16]
101538863  [KO:K07413] [EC:1.14.14.1]
101539080  F2RL1; proteinase-activated receptor 2 [KO:K04234]
101539126  [KO:K07413] [EC:1.14.14.1]
101539279  PRKCG; protein kinase C gamma type isoform X1 [KO:K19663] [EC:2.7.11.13]
101539349  PRKCH; protein kinase C eta type [KO:K18051] [EC:2.7.11.13]
101539413  ADCY2; LOW QUALITY PROTEIN: adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
101539470  [KO:K04632]
101539723  BDKRB2; B2 bradykinin receptor [KO:K03916]
101539748  [KO:K07413] [EC:1.14.14.1]
101539776  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
101539926  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
101539989  BDKRB1; B1 bradykinin receptor [KO:K03915]
101540028  ASIC5; acid-sensing ion channel 5 [KO:K04832]
101540186  [KO:K07413] [EC:1.14.14.1]
101540859  NTRK1; high affinity nerve growth factor receptor [KO:K03176] [EC:2.7.10.1]
101540938  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
101541147  KNG1; kininogen-1 [KO:K03898]
101541249  [KO:K07413] [EC:1.14.14.1]
101541555  CALM2; calmodulin [KO:K02183]
101541695  [KO:K07413] [EC:1.14.14.1]
101541868  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
101542258  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma [KO:K04515] [EC:2.7.11.17]
101542671  [KO:K07413] [EC:1.14.14.1]
101542741  PTGER4; prostaglandin E2 receptor EP4 subtype [KO:K04261]
101542881  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
101542897  [KO:K07425] [EC:1.14.14.80]
101542917  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
101543012  HTR2A; 5-hydroxytryptamine receptor 2A [KO:K04157]
101543045  PRKCE; protein kinase C epsilon type [KO:K18050] [EC:2.7.11.13]
101543177  [KO:K07425] [EC:1.14.14.80]
101543498  PLA2G4A; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
101543858  ADCY7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
101543973  [KO:K02183]
101544925  TRPA1; transient receptor potential cation channel subfamily A member 1 [KO:K04984]
101544951  ASIC2; acid-sensing ion channel 2 [KO:K04828]
101545302  CALML5; calmodulin-like protein 5 [KO:K02183]
101545321  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
101545625  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
101545860  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X2 [KO:K01116] [EC:3.1.4.11]
101545883  P2RY2; P2Y purinoceptor 2 [KO:K04269]
101545907  [KO:K07413] [EC:1.14.14.1]
101546049  [KO:K07413] [EC:1.14.14.1]
101546518  [KO:K07413] [EC:1.14.14.1]
101546657  TRPV4; transient receptor potential cation channel subfamily V member 4 isoform X1 [KO:K04973]
101546696  [KO:K04345] [EC:2.7.11.11]
101546811  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
101546941  CALML4; calmodulin-like protein 4 [KO:K02183]
101547055  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
101547106  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
101547147  [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
101547220  ALOX12; arachidonate 12-lipoxygenase, 12S-type [KO:K00458] [EC:1.13.11.31]
101547409  [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
101547469  [KO:K07413] [EC:1.14.14.1]
101547484  [KO:K00458] [EC:1.13.11.31]
101547658  PRKCB; protein kinase C beta type isoform X2 [KO:K19662] [EC:2.7.11.13]
101547677  [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
101547690  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
101547708  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
101547815  ASIC3; acid-sensing ion channel 3 [KO:K04830]
101547951  [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
101548002  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
101548282  [KO:K07413] [EC:1.14.14.1]
101548304  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
101548728  [KO:K07413] [EC:1.14.14.1]
101548987  [KO:K07413] [EC:1.14.14.1]
101549131  ADCY6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
101549253  [KO:K07413] [EC:1.14.14.1]
101549522  [KO:K07413] [EC:1.14.14.1]
101549525  [KO:K07413] [EC:1.14.14.1]
101549665  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
101549827  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
101550043  [KO:K07413] [EC:1.14.14.1]
101550075  IL1B; interleukin-1 beta [KO:K04519]
101550559  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
101550881  ASIC4; acid-sensing ion channel 4 [KO:K04831]
101551078  [KO:K07425] [EC:1.14.14.80]
101551223  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
101551730  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
101551819  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
101551866  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
101551961  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
101552535  CALML3; calmodulin-like protein 3 [KO:K02183]
101553765  PRKCQ; protein kinase C theta type isoform X1 [KO:K18052] [EC:2.7.11.13]
101553892  TRPV2; transient receptor potential cation channel subfamily V member 2 [KO:K04971]
101553999  PTGER2; prostaglandin E2 receptor EP2 subtype [KO:K04259]
101554044  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
101554088  PLCG2; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
101554190  IGF1; insulin-like growth factor I isoform X4 [KO:K05459]
101554401  CALM1; calmodulin isoform X1 [KO:K02183]
101554482  HTR2B; 5-hydroxytryptamine receptor 2B [KO:K04157]
101554719  [KO:K04345] [EC:2.7.11.11]
101555205  PLA2G4B; cytosolic phospholipase A2 beta [KO:K16342] [EC:3.1.1.4]
101555435  ASIC1; acid-sensing ion channel 1 isoform X1 [KO:K04829]
101555471  PLA2G4D; cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
101555578  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
101555733  PLA2G4F; cytosolic phospholipase A2 zeta [KO:K16342] [EC:3.1.1.4]
101555912  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 isoform X1 [KO:K04432] [EC:2.7.12.2]
101555935  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
101556063  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
101556467  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
101556557  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
101556597  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
101556630  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
101557190  NGF; beta-nerve growth factor [KO:K02582]
101557362  HTR2C; 5-hydroxytryptamine receptor 2C [KO:K04157]
101557523  PLA2G4E; cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]
101557528  PLA2G6; 85/88 kDa calcium-independent phospholipase A2 isoform X1 [KO:K16343] [EC:3.1.1.4]
101557809  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
101557843  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
101558069  TRPM8; transient receptor potential cation channel subfamily M member 8 [KO:K04983]
101558147  [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
101558420  [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
101558845  IL1RAP; interleukin-1 receptor accessory protein isoform X1 [KO:K04723]
101558898  HRH1; histamine H1 receptor [KO:K04149]
101559065  SRC; proto-oncogene tyrosine-protein kinase Src isoform X2 [KO:K05704] [EC:2.7.10.2]
101559179  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
101559307  CALM3; calmodulin [KO:K02183]
105943477  [KO:K07413] [EC:1.14.14.1]
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
  Authors
Wang H, Woolf CJ
  Title
Pain TRPs.
  Journal
Neuron 46:9-12 (2005)
DOI:10.1016/j.neuron.2005.03.011
Reference
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
sara00590  Arachidonic acid metabolism
sara04010  MAPK signaling pathway
sara04020  Calcium signaling pathway
KO pathway
ko04750   

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