KEGG   PATHWAY: pale04750
Entry
pale04750                   Pathway                                
Name
Inflammatory mediator regulation of TRP channels - Pteropus alecto (black flying fox)
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
pale04750  Inflammatory mediator regulation of TRP channels
pale04750

Other DBs
GO: 0019233
Organism
Pteropus alecto (black flying fox) [GN:pale]
Gene
102885643  KNG1; kininogen-1 isoform X1 [KO:K03898]
102895893  B2 bradykinin receptor isoform X1 [KO:K03916]
102886552  HTR2B; 5-hydroxytryptamine receptor 2B [KO:K04157]
102887090  HTR2C; 5-hydroxytryptamine receptor 2C isoform X1 [KO:K04157]
102891388  HTR2A; 5-hydroxytryptamine receptor 2A [KO:K04157]
102890827  HRH1; histamine H1 receptor [KO:K04149]
102890140  P2RY2; P2Y purinoceptor 2 [KO:K04269]
102889217  P2Y purinoceptor 2-like [KO:K04269]
102877919  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
102883421  PLA2G4F; cytosolic phospholipase A2 zeta [KO:K16342] [EC:3.1.1.4]
102883684  PLA2G4E; cytosolic phospholipase A2 epsilon isoform X2 [KO:K16342] [EC:3.1.1.4]
102887778  PLA2G4D; cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
102886310  PLA2G4A; cytosolic phospholipase A2 isoform X1 [KO:K16342] [EC:3.1.1.4]
102888274  cytosolic phospholipase A2 beta [KO:K16342] [EC:3.1.1.4]
102880597  PLA2G6; 85/88 kDa calcium-independent phospholipase A2 isoform X3 [KO:K16343] [EC:3.1.1.4]
102897481  ALOX12; arachidonate 12-lipoxygenase, 12S-type [KO:K00458] [EC:1.13.11.31]
102879238  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
102885207  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
102885781  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
102885953  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
102894982  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
102896356  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
102881783  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
102894641  PRKCE; protein kinase C epsilon type [KO:K18050] [EC:2.7.11.13]
102892254  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
102881448  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
102887827  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
102890773  TRPA1; transient receptor potential cation channel subfamily A member 1 [KO:K04984]
102899034  TRPV1; transient receptor potential cation channel subfamily V member 1 isoform X1 [KO:K05222]
102881296  ASIC1; acid-sensing ion channel 1 isoform X1 [KO:K04829]
102897807  ASIC2; acid-sensing ion channel 2 [KO:K04828]
102879442  ASIC3; acid-sensing ion channel 3 isoform X3 [KO:K04830]
102897252  ASIC4; LOW QUALITY PROTEIN: acid-sensing ion channel 4 [KO:K04831]
102890174  ASIC5; acid-sensing ion channel 5 [KO:K04832]
102894226  CALM2; calmodulin-2 isoform X1 [KO:K02183]
102897273  CALM3; calmodulin-3 [KO:K02183]
102886058  CALM1; calmodulin-1 [KO:K02183]
102884196  CALML6; calmodulin-like protein 6 [KO:K02183]
102891673  calmodulin-like [KO:K02183]
102893109  CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183]
102881744  calmodulin-like [KO:K02183]
102888982  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta [KO:K04515] [EC:2.7.11.17]
102888385  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
102880869  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta [KO:K04515] [EC:2.7.11.17]
102896030  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma [KO:K04515] [EC:2.7.11.17]
102893238  IL1B; interleukin-1 beta [KO:K04519]
102884439  IL1R1; interleukin-1 receptor type 1 isoform X1 [KO:K04386]
102892819  IL1RAP; interleukin-1 receptor accessory protein isoform X1 [KO:K04723]
102886389  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 isoform X1 [KO:K04432] [EC:2.7.12.2]
102888822  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
102895900  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
102888602  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
102888845  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
102877720  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
102885064  MAPK10; mitogen-activated protein kinase 10 isoform X5 [KO:K04440] [EC:2.7.11.24]
102890689  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
102892777  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
102885454  NGF; beta-nerve growth factor [KO:K02582]
112472150  NTRK1; high affinity nerve growth factor receptor [KO:K03176] [EC:2.7.10.1]
102896228  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
102883128  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
102889227  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
102880320  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
102889576  PIK3CD; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
102879163  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
102891637  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X3 [KO:K02649]
102879453  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
102888600  PRKCD; protein kinase C delta type [KO:K06068] [EC:2.7.11.13]
102891249  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
102892835  TRPM8; LOW QUALITY PROTEIN: transient receptor potential cation channel subfamily M member 8 [KO:K04983]
102884861  PTGER2; prostaglandin E2 receptor EP2 subtype [KO:K04259]
102886026  PTGER4; prostaglandin E2 receptor EP4 subtype [KO:K04261]
102889764  guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas [KO:K04632]
102884106  neuroendocrine secretory protein 55-like [KO:K04632]
102887497  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
102893265  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
102886232  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
102890575  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
102897495  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
102890588  ADCY6; adenylate cyclase type 6 isoform X2 [KO:K08046] [EC:4.6.1.1]
102881535  ADCY7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
102896789  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
102885676  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
102886679  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
102877853  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
102885612  TRPV4; transient receptor potential cation channel subfamily V member 4 [KO:K04973]
102892595  F2RL1; proteinase-activated receptor 2 isoform X2 [KO:K04234]
102891905  cytochrome P450 2C19 [KO:K07413] [EC:1.14.14.1]
102885276  cytochrome P450 2J2 [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
102887078  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
102880663  PRKCB; protein kinase C beta type [KO:K19662] [EC:2.7.11.13]
102888961  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
102897040  PRKCH; protein kinase C eta type isoform X1 [KO:K18051] [EC:2.7.11.13]
102892408  PRKCQ; protein kinase C theta type [KO:K18052] [EC:2.7.11.13]
102890331  IGF1; insulin-like growth factor I isoform X3 [KO:K05459]
102892909  TRPV2; transient receptor potential cation channel subfamily V member 2 [KO:K04971]
102898613  TRPV3; transient receptor potential cation channel subfamily V member 3 isoform X1 [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
pale00590  Arachidonic acid metabolism
pale04010  MAPK signaling pathway
pale04020  Calcium signaling pathway
KO pathway
ko04750   
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