KEGG   PATHWAY: pvp04750
Entry
pvp04750                    Pathway                                
Name
Inflammatory mediator regulation of TRP channels - Pteropus vampyrus (large 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
pvp04750  Inflammatory mediator regulation of TRP channels
pvp04750

Other DBs
GO: 0019233
Organism
Pteropus vampyrus (large flying fox) [GN:pvp]
Gene
105288318  PLA2G6; 85/88 kDa calcium-independent phospholipase A2 [KO:K16343] [EC:3.1.1.4]
105288668  PLA2G4D; cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
105288669  PLA2G4F; cytosolic phospholipase A2 zeta isoform X2 [KO:K16342] [EC:3.1.1.4]
105288781  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
105288785  PLA2G4B; cytosolic phospholipase A2 beta [KO:K16342] [EC:3.1.1.4]
105288787  PLA2G4E; cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]
105288850  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
105288866  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X2 [KO:K04515] [EC:2.7.11.17]
105288933  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
105289063  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
105289220  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
105289628  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
105289813  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
105289863  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
105290127  CALM1; calmodulin-1 [KO:K02183]
105291028  ASIC4; LOW QUALITY PROTEIN: acid-sensing ion channel 4 [KO:K04831]
105291296  TRPV2; transient receptor potential cation channel subfamily V member 2 isoform X1 [KO:K04971]
105291818  TRPV1; transient receptor potential cation channel subfamily V member 1 isoform X1 [KO:K05222]
105291820  TRPV3; transient receptor potential cation channel subfamily V member 3 isoform X1 [KO:K04972]
105291965  ASIC2; acid-sensing ion channel 2 isoform X1 [KO:K04828]
105291977  ALOX12; arachidonate 12-lipoxygenase, 12S-type [KO:K00458] [EC:1.13.11.31]
105292087  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
105292197  ASIC5; acid-sensing ion channel 5 [KO:K04832]
105292913  CALM2; calmodulin-2 isoform X1 [KO:K02183]
105292973  PRKCE; protein kinase C epsilon type [KO:K18050] [EC:2.7.11.13]
105294112  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
105295052  PLA2G4A; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
105295171  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
105296083  [KO:K04632]
105296416  NTRK1; high affinity nerve growth factor receptor [KO:K03176] [EC:2.7.10.1]
105296475  NGF; beta-nerve growth factor isoform X2 [KO:K02582]
105296513  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
105296521  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 [KO:K01116] [EC:3.1.4.11]
105296605  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
105296708  TRPA1; transient receptor potential cation channel subfamily A member 1 [KO:K04984]
105297140  [KO:K02649]
105297322  CALM3; calmodulin-3 [KO:K02183]
105297518  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
105297556  ASIC1; acid-sensing ion channel 1 isoform X1 [KO:K04829]
105297702  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
105297846  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
105298727  IL1R1; interleukin-1 receptor type 1 isoform X1 [KO:K04386]
105298737  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
105298795  BDKRB1; B1 bradykinin receptor [KO:K03915]
105298796  BDKRB2; B2 bradykinin receptor [KO:K03916]
105298936  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
105299028  HRH1; histamine H1 receptor [KO:K04149]
105299098  PTGER4; prostaglandin E2 receptor EP4 subtype [KO:K04261]
105299132  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit isoform X1 [KO:K06269] [EC:3.1.3.16]
105299180  [KO:K02183]
105299371  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X3 [KO:K02649]
105299441  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha [KO:K04515] [EC:2.7.11.17]
105299444  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
105299581  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
105299978  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
105300015  HTR2A; 5-hydroxytryptamine receptor 2A [KO:K04157]
105300246  TRPM8; transient receptor potential cation channel subfamily M member 8 [KO:K04983]
105301035  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
105301036  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
105301042  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
105301250  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
105301394  [KO:K07413] [EC:1.14.14.1]
105301608  HTR2C; 5-hydroxytryptamine receptor 2C [KO:K04157]
105302170  F2RL1; proteinase-activated receptor 2 isoform X2 [KO:K04234]
105302452  [KO:K04634]
105302767  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta [KO:K04515] [EC:2.7.11.17]
105303095  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
105303444  [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
105303606  CALML6; calmodulin-like protein 6 [KO:K02183]
105303649  P2RY2; P2Y purinoceptor 2 isoform X1 [KO:K04269]
105303751  ASIC3; acid-sensing ion channel 3 isoform X3 [KO:K04830]
105303963  TRPV4; LOW QUALITY PROTEIN: transient receptor potential cation channel subfamily V member 4 [KO:K04973]
105303982  IL1B; interleukin-1 beta [KO:K04519]
105304165  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
105304348  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
105306132  HTR2B; 5-hydroxytryptamine receptor 2B [KO:K04157]
105306481  IL1RAP; interleukin-1 receptor accessory protein isoform X1 [KO:K04723]
105306731  KNG1; kininogen-1 isoform X1 [KO:K03898]
105307215  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
105307575  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
105308283  [KO:K04441] [EC:2.7.11.24]
105308299  [KO:K08041] [EC:4.6.1.1]
105308501  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
105308675  [KO:K18052] [EC:2.7.11.13]
105308762  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta [KO:K04515] [EC:2.7.11.17]
105308818  [KO:K19662] [EC:2.7.11.13]
105308956  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X2 [KO:K00922] [EC:2.7.1.153]
105309351  PTGER2; prostaglandin E2 receptor EP2 subtype isoform X1 [KO:K04259]
105309400  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
105309462  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
105309689  CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183]
105309924  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
105310014  PRKCH; protein kinase C eta type [KO:K18051] [EC:2.7.11.13]
105310714  IGF1; insulin-like growth factor I isoform X3 [KO:K05459]
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
pvp00590  Arachidonic acid metabolism
pvp04010  MAPK signaling pathway
pvp04020  Calcium signaling pathway
KO pathway
ko04750   

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