KEGG   PATHWAY: umr04750
Entry
umr04750                    Pathway                                
Name
Inflammatory mediator regulation of TRP channels - Ursus maritimus (polar 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
umr04750  Inflammatory mediator regulation of TRP channels
umr04750

Other DBs
GO: 0019233
Organism
Ursus maritimus (polar bear) [GN:umr]
Gene
103676052  KNG1; kininogen-1 isoform X1 [KO:K03898]
103673646  BDKRB1; B1 bradykinin receptor [KO:K03915]
103669660  BDKRB2; B2 bradykinin receptor [KO:K03916]
103662679  HTR2B; 5-hydroxytryptamine receptor 2B [KO:K04157]
103677593  HTR2A; 5-hydroxytryptamine receptor 2A isoform X1 [KO:K04157]
103679732  HTR2C; 5-hydroxytryptamine receptor 2C [KO:K04157]
103669552  HRH1; histamine H1 receptor [KO:K04149]
103678112  P2RY2; P2Y purinoceptor 2 [KO:K04269]
103663281  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
103668635  PLA2G4A; cytosolic phospholipase A2 isoform X1 [KO:K16342] [EC:3.1.1.4]
103673432  PLA2G4E; cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]
103673531  PLA2G4F; cytosolic phospholipase A2 zeta [KO:K16342] [EC:3.1.1.4]
103673532  PLA2G4D; cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
103676531  PLA2G6; 85/88 kDa calcium-independent phospholipase A2 isoform X1 [KO:K16343] [EC:3.1.1.4]
103660455  ALOX12; polyunsaturated fatty acid lipoxygenase ALOX12 isoform X1 [KO:K00458] [EC:1.13.11.31]
103673552  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
103674425  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
103674426  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
103679549  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
121099746  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
103669597  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
103665275  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
103665553  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
103671225  PRKCE; protein kinase C epsilon type [KO:K18050] [EC:2.7.11.13]
103661277  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
103679611  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
103671909  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
103681282  TRPA1; transient receptor potential cation channel subfamily A member 1 [KO:K04984]
103667135  TRPV1; transient receptor potential cation channel subfamily V member 1 [KO:K05222]
103675470  ASIC1; acid-sensing ion channel 1 isoform X1 [KO:K04829]
103667269  ASIC2; acid-sensing ion channel 2 isoform X2 [KO:K04828]
103660956  ASIC3; acid-sensing ion channel 3 isoform X1 [KO:K04830]
103662873  ASIC4; acid-sensing ion channel 4 isoform X1 [KO:K04831]
103658101  ASIC5; acid-sensing ion channel 5 [KO:K04832]
103670304  CALM1; calmodulin-1 isoform X1 [KO:K02183]
103682041  CALML6; calmodulin-like protein 6 [KO:K02183]
103676238  calmodulin [KO:K02183]
103676239  CALML3; calmodulin-like protein 3 [KO:K02183]
103671240  CALM2; calmodulin-2 [KO:K02183]
103679049  CALML4; calmodulin-like protein 4 isoform X3 [KO:K02183]
103657204  CALM3; calmodulin-3 [KO:K02183]
103661761  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X3 [KO:K04515] [EC:2.7.11.17]
103664598  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha [KO:K04515] [EC:2.7.11.17]
103668027  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
103674683  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
103671495  IL1B; interleukin-1 beta isoform X2 [KO:K04519]
103670641  IL1R1; interleukin-1 receptor type 1 isoform X1 [KO:K04386]
103676019  interleukin-1 receptor accessory protein isoform X2 [KO:K04723]
103658475  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
103665687  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
103674115  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
103665451  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
103665538  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
103674004  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
103676947  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
103679990  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
103667893  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
103669449  NGF; beta-nerve growth factor [KO:K02582]
103669754  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
103662093  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X1 [KO:K05859] [EC:3.1.4.11]
103678592  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
103666874  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
103676125  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
103675162  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
103663617  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X3 [KO:K02649]
103670766  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
103674744  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
103669776  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
103662653  TRPM8; transient receptor potential cation channel subfamily M member 8 [KO:K04983]
103672874  PTGER2; prostaglandin E2 receptor EP2 subtype [KO:K04259]
103664680  PTGER4; prostaglandin E2 receptor EP4 subtype [KO:K04261]
103670935  LOW QUALITY PROTEIN: guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas [KO:K04632]
103670936  neuroendocrine secretory protein 55 [KO:K04632]
103674675  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
103679250  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
103671685  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
103679331  ADCY4; adenylate cyclase type 4 isoform X2 [KO:K08044] [EC:4.6.1.1]
103678826  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
103675618  ADCY6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
103673916  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
103661704  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
103668547  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
103662972  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
103682183  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
103678292  TRPV4; transient receptor potential cation channel subfamily V member 4 [KO:K04973]
103663553  proteinase-activated receptor 2 isoform X3 [KO:K04234]
103670756  cytochrome P450 2C21 [KO:K07413] [EC:1.14.14.1]
103659697  cytochrome P450 2C23-like [KO:K07413] [EC:1.14.14.1]
103663082  cytochrome P450 2J2 [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
103670742  cytochrome P450 4A6 [KO:K07425] [EC:1.14.14.80]
103665907  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
103668895  PRKCB; LOW QUALITY PROTEIN: protein kinase C beta type [KO:K19662] [EC:2.7.11.13]
103672914  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
103672479  PRKCH; protein kinase C eta type isoform X1 [KO:K18051] [EC:2.7.11.13]
103676251  PRKCQ; protein kinase C theta type isoform X1 [KO:K18052] [EC:2.7.11.13]
103676495  IGF1; insulin-like growth factor I isoform X1 [KO:K05459]
103658520  TRPV2; transient receptor potential cation channel subfamily V member 2 isoform X1 [KO:K04971]
103667136  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
umr00590  Arachidonic acid metabolism
umr04010  MAPK signaling pathway
umr04020  Calcium signaling pathway
KO pathway
ko04750   
LinkDB

DBGET integrated database retrieval system