KEGG   PATHWAY: uar04750
Entry
uar04750                    Pathway                                
Name
Inflammatory mediator regulation of TRP channels - Ursus americanus (American black bear)
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
uar04750  Inflammatory mediator regulation of TRP channels
uar04750

Other DBs
GO: 0019233
Organism
Ursus americanus (American black bear) [GN:uar]
Gene
123801268  KNG1; kininogen-1 isoform X1 [KO:K03898]
123803924  BDKRB1; B1 bradykinin receptor [KO:K03915]
123803922  BDKRB2; B2 bradykinin receptor [KO:K03916]
123790080  HTR2B; 5-hydroxytryptamine receptor 2B [KO:K04157]
123797203  HTR2C; 5-hydroxytryptamine receptor 2C [KO:K04157]
123791836  HTR2A; 5-hydroxytryptamine receptor 2A [KO:K04157]
123799216  HRH1; histamine H1 receptor [KO:K04149]
123804186  P2RY2; P2Y purinoceptor 2 isoform X1 [KO:K04269]
123781527  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha isoform X1 [KO:K04634]
123801377  PLA2G4A; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
123803827  PLA2G4B; cytosolic phospholipase A2 beta [KO:K16342] [EC:3.1.1.4]
123803837  PLA2G4F; cytosolic phospholipase A2 zeta [KO:K16342] [EC:3.1.1.4]
123775802  PLA2G4E; cytosolic phospholipase A2 epsilon isoform X1 [KO:K16342] [EC:3.1.1.4]
123776483  PLA2G4D; cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
123780588  PLA2G6; 85/88 kDa calcium-independent phospholipase A2 isoform X1 [KO:K16343] [EC:3.1.1.4]
123792172  ALOX12; polyunsaturated fatty acid lipoxygenase ALOX12 [KO:K00458] [EC:1.13.11.31]
123799710  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
123799736  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
123804253  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
123778465  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
123799165  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
123801684  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
123790908  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
123785895  PRKCE; protein kinase C epsilon type [KO:K18050] [EC:2.7.11.13]
123799882  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
123795174  serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
123778467  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
123779126  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
123800478  TRPA1; transient receptor potential cation channel subfamily A member 1 [KO:K04984]
123776990  TRPV1; transient receptor potential cation channel subfamily V member 1 isoform X1 [KO:K05222]
123794755  ASIC1; acid-sensing ion channel 1 isoform X1 [KO:K04829]
123777051  ASIC2; acid-sensing ion channel 2 [KO:K04828]
123788777  ASIC3; acid-sensing ion channel 3 isoform X1 [KO:K04830]
123779455  ASIC4; acid-sensing ion channel 4 isoform X1 [KO:K04831]
123793046  ASIC5; acid-sensing ion channel 5 [KO:K04832]
123785908  CALM2; calmodulin-2 [KO:K02183]
123800842  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
123802291  calmodulin-like [KO:K02183]
123802321  CALML3; calmodulin-like protein 3 [KO:K02183]
123796079  CALML6; calmodulin-like protein 6 [KO:K02183]
123798898  CALM1; calmodulin-1 [KO:K02183]
123778741  CALM3; calmodulin-3 [KO:K02183]
123793341  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
123803651  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
123789460  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
123782837  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
123799741  IL1B; interleukin-1 beta [KO:K04519]
123775960  IL1R1; interleukin-1 receptor type 1 isoform X1 [KO:K04386]
123801281  interleukin-1 receptor accessory protein isoform X1 [KO:K04723]
123779716  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
123803240  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
123803776  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
123803793  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
123776209  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
123776212  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
123800287  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
123788054  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
123790496  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
123794928  NGF; beta-nerve growth factor [KO:K02582]
123783398  NTRK1; high affinity nerve growth factor receptor isoform X1 [KO:K03176] [EC:2.7.10.1]
123796994  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
123791349  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X1 [KO:K05859] [EC:3.1.4.11]
123786407  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
123788422  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
123779078  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
123800228  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
123793748  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
123779926  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
123798757  PRKCD; protein kinase C delta type [KO:K06068] [EC:2.7.11.13]
123796968  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
123790116  TRPM8; transient receptor potential cation channel subfamily M member 8 [KO:K04983]
123800669  PTGER2; prostaglandin E2 receptor EP2 subtype [KO:K04259]
123785506  PTGER4; prostaglandin E2 receptor EP4 subtype [KO:K04261]
123803297  neuroendocrine secretory protein 55 [KO:K04632]
123803290  LOW QUALITY PROTEIN: guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas-like [KO:K04632]
123789481  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
123791264  ADCY2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
123799951  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
123795737  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
123802178  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
123794794  ADCY6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
123798393  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
123801897  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
123783548  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
123801768  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
123795272  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
123788209  TRPV4; transient receptor potential cation channel subfamily V member 4 isoform X1 [KO:K04973]
123791555  F2RL1; proteinase-activated receptor 2 isoform X1 [KO:K04234]
123800006  cytochrome P450 2C23-like [KO:K07413] [EC:1.14.14.1]
123800347  cytochrome P450 2C41-like isoform X1 [KO:K07413] [EC:1.14.14.1]
123783991  LOW QUALITY PROTEIN: cytochrome P450 2C21-like [KO:K07413] [EC:1.14.14.1]
123783992  cytochrome P450 2C21-like [KO:K07413] [EC:1.14.14.1]
123783994  cytochrome P450 2C21-like [KO:K07413] [EC:1.14.14.1]
123791300  cytochrome P450 2C41-like [KO:K07413] [EC:1.14.14.1]
123777781  cytochrome P450 2C41-like [KO:K07413] [EC:1.14.14.1]
123795371  cytochrome P450 2J2 [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
123793725  cytochrome P450 4A6 isoform X1 [KO:K07425] [EC:1.14.14.80]
123793728  cytochrome P450 4A6-like isoform X1 [KO:K07425] [EC:1.14.14.80]
123803224  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
123778823  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
123786995  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
123800656  PRKCH; protein kinase C eta type isoform X1 [KO:K18051] [EC:2.7.11.13]
123802334  PRKCQ; protein kinase C theta type isoform X1 [KO:K18052] [EC:2.7.11.13]
123780774  IGF1; insulin-like growth factor I isoform X1 [KO:K05459]
123779763  TRPV2; transient receptor potential cation channel subfamily V member 2 isoform X1 [KO:K04971]
123777030  TRPV3; transient receptor potential cation channel subfamily V member 3 [KO:K04972]
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
uar00590  Arachidonic acid metabolism
uar04010  MAPK signaling pathway
uar04020  Calcium signaling pathway
KO pathway
ko04750   
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