KEGG   PATHWAY: mcc04750
Entry
mcc04750                    Pathway                                
Name
Inflammatory mediator regulation of TRP channels - Macaca mulatta (rhesus monkey)
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
mcc04750  Inflammatory mediator regulation of TRP channels
mcc04750

Other DBs
GO: 0019233
Organism
Macaca mulatta (rhesus monkey) [GN:mcc]
Gene
100424240  CYP2C76; cytochrome P450, family 2, subfamily C, polypeptide 76 precursor [KO:K07413] [EC:1.14.14.1]
100424593  PLA2G4E; cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]
100424899  [KO:K04632]
100429414  TRPM8; transient receptor potential cation channel subfamily M member 8 [KO:K04983]
100533113  PLA2G4B; cytosolic phospholipase A2 beta [KO:K16342] [EC:3.1.1.4]
574387  IL1RAP; interleukin-1 receptor accessory protein precursor [KO:K04723]
613032  HTR2A; 5-hydroxytryptamine receptor 2A [KO:K04157]
693523  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
693631  [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
693753  CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183]
693914  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
694289  [KO:K04632]
694623  TRPA1; transient receptor potential cation channel subfamily A member 1 [KO:K04984]
694656  PRKCD; protein kinase C delta type [KO:K06068] [EC:2.7.11.13]
694730  ADCY7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
695220  PTGER4; prostaglandin E2 receptor EP4 subtype [KO:K04261]
695328  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
695792  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
695986  TRPV2; transient receptor potential cation channel subfamily V member 2 isoform X1 [KO:K04971]
696359  HRH1; histamine H1 receptor [KO:K04149]
697069  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
697230  ADCY1; adenylate cyclase type 1 isoform X1 [KO:K08041] [EC:4.6.1.1]
698444  IGF1; insulin-like growth factor I precursor [KO:K05459]
698552  CALM1; calmodulin-1 isoform X1 [KO:K02183]
698996  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
699617  ASIC5; acid-sensing ion channel 5 [KO:K04832]
699736  MAPK10; mitogen-activated protein kinase 10 isoform 1 [KO:K04440] [EC:2.7.11.24]
700184  PLA2G6; 85/88 kDa calcium-independent phospholipase A2 isoform X1 [KO:K16343] [EC:3.1.1.4]
700652  PRKACG; cAMP-dependent protein kinase catalytic subunit gamma [KO:K04345] [EC:2.7.11.11]
701057  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
701195  PRKCB; protein kinase C beta type [KO:K19662] [EC:2.7.11.13]
701951  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
702504  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X2 [KO:K04515] [EC:2.7.11.17]
703302  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
703514  CALML6; calmodulin-like protein 6 isoform X1 [KO:K02183]
703669  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
703698  BDKRB2; B2 bradykinin receptor [KO:K03916]
703972  ASIC4; LOW QUALITY PROTEIN: acid-sensing ion channel 4 [KO:K04831]
704356  PRKCH; protein kinase C eta type [KO:K18051] [EC:2.7.11.13]
704701  IL1B; interleukin-1 beta precursor [KO:K04519]
705195  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
705680  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
705980  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma [KO:K04515] [EC:2.7.11.17]
706351  [KO:K02183]
706789  ADCY9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
706977  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X11 [KO:K04515] [EC:2.7.11.17]
707310  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
707466  KNG1; kininogen-1 [KO:K03898]
707479  F2RL1; proteinase-activated receptor 2 [KO:K04234]
707592  PLA2G4D; cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
707690  PLA2G4F; cytosolic phospholipase A2 zeta isoform X1 [KO:K16342] [EC:3.1.1.4]
707978  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
708024  PTGER2; prostaglandin E2 receptor EP2 subtype [KO:K04259]
708141  HTR2C; 5-hydroxytryptamine receptor 2C isoform X1 [KO:K04157]
708714  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
709605  TRPV4; transient receptor potential cation channel subfamily V member 4 isoform X1 [KO:K04973]
709728  PRKACB; cAMP-dependent protein kinase catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
709935  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
709959  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
710540  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
710552  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
711115  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
711681  NGF; beta-nerve growth factor [KO:K02582]
711726  IL1R1; interleukin-1 receptor type 1 [KO:K04386]
711808  HTR2B; 5-hydroxytryptamine receptor 2B isoform X1 [KO:K04157]
712159  CALML5; calmodulin-like protein 5 [KO:K02183]
712251  BDKRB1; B1 bradykinin receptor [KO:K03915]
713320  ASIC1; acid-sensing ion channel 1 [KO:K04829]
713683  [KO:K00458] [EC:1.13.11.31]
713748  ALOX12; arachidonate 12-lipoxygenase, 12S-type [KO:K00458] [EC:1.13.11.31]
714173  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X1 [KO:K05859] [EC:3.1.4.11]
714396  ASIC3; acid-sensing ion channel 3 isoform X1 [KO:K04830]
714533  PRKCE; protein kinase C epsilon type [KO:K18050] [EC:2.7.11.13]
714684  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
715270  CALM2; calmodulin-2 [KO:K02183]
715745  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
715782  MAPK9; mitogen-activated protein kinase 9 isoform X2 [KO:K04440] [EC:2.7.11.24]
715794  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
715897  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
716098  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
716584  CALM3; calmodulin-3 isoform X1 [KO:K02183]
716635  PLA2G4A; cytosolic phospholipase A2 isoform X1 [KO:K16342] [EC:3.1.1.4]
717686  [KO:K02183]
717764  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
718040  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
718204  ASIC2; acid-sensing ion channel 2 [KO:K04828]
718387  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
718412  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
718418  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X3 [KO:K05858] [EC:3.1.4.11]
718510  [KO:K16342] [EC:3.1.1.4]
718603  P2RY2; P2Y purinoceptor 2 [KO:K04269]
718632  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
718976  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
719085  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
719367  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
719670  NTRK1; high affinity nerve growth factor receptor isoform X3 [KO:K03176] [EC:2.7.10.1]
720263  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
721450  TRPV3; transient receptor potential cation channel subfamily V member 3 isoform X1 [KO:K04972]
721455  TRPV1; transient receptor potential cation channel subfamily V member 1 [KO:K05222]
721735  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
722513  CALML3; calmodulin-like protein 3 [KO:K02183]
722559  PRKCQ; protein kinase C theta type [KO:K18052] [EC:2.7.11.13]
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
mcc00590  Arachidonic acid metabolism
mcc04010  MAPK signaling pathway
mcc04020  Calcium signaling pathway
KO pathway
ko04750   

DBGET integrated database retrieval system