KEGG   PATHWAY: biu04750
Entry
biu04750                    Pathway                                
Name
Inflammatory mediator regulation of TRP channels - Bos indicus (zebu cattle)
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
biu04750  Inflammatory mediator regulation of TRP channels
biu04750

Other DBs
GO: 0019233
Organism
Bos indicus (zebu cattle) [GN:biu]
Gene
109562726  kininogen-1-like [KO:K03898]
109575240  BDKRB1; B1 bradykinin receptor [KO:K03915]
109575666  BDKRB2; B2 bradykinin receptor [KO:K03916]
109571939  HTR2B; 5-hydroxytryptamine receptor 2B [KO:K04157]
109566702  HTR2A; 5-hydroxytryptamine receptor 2A [KO:K04157]
109554842  HTR2C; LOW QUALITY PROTEIN: 5-hydroxytryptamine receptor 2C [KO:K04157]
109576355  HRH1; histamine H1 receptor [KO:K04149]
109569646  P2RY2; P2Y purinoceptor 2 [KO:K04269]
109562978  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
109570696  PLA2G4A; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
109564977  PLA2G4B; cytosolic phospholipase A2 beta [KO:K16342] [EC:3.1.1.4]
109564980  PLA2G4E; cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]
109564981  PLA2G4D; cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
109564982  PLA2G4F; cytosolic phospholipase A2 zeta [KO:K16342] [EC:3.1.1.4]
109559808  PLA2G6; 85/88 kDa calcium-independent phospholipase A2 isoform X1 [KO:K16343] [EC:3.1.1.4]
109574004  ALOX12; arachidonate 12-lipoxygenase, 12S-type isoform X1 [KO:K00458] [EC:1.13.11.31]
109554384  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
109567852  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
109567854  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
109564927  PLCB2; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
109576135  ITPR1; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
109558547  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
109576552  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
109566044  PRKCE; protein kinase C epsilon type [KO:K18050] [EC:2.7.11.13]
109554414  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
109571193  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
109566263  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
109574565  TRPV1; transient receptor potential cation channel subfamily V member 1 [KO:K05222]
109559118  ASIC1; acid-sensing ion channel 1 isoform X1 [KO:K04829]
109573181  ASIC2; acid-sensing ion channel 2 [KO:K04828]
109557797  ASIC3; LOW QUALITY PROTEIN: acid-sensing ion channel 3 [KO:K04830]
109571180  ASIC4; LOW QUALITY PROTEIN: acid-sensing ion channel 4 [KO:K04831]
109570891  ASIC5; acid-sensing ion channel 5 [KO:K04832]
109565417  CALM1; calmodulin [KO:K02183]
109575003  calmodulin-alpha-like [KO:K02183]
109566056  CALM2; calmodulin [KO:K02183]
109568081  calmodulin-like [KO:K02183]
109570679  CALML6; LOW QUALITY PROTEIN: calmodulin-like protein 6 [KO:K02183]
109572535  CALM3; calmodulin isoform X1 [KO:K02183]
109564712  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
109553698  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
109560236  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
109557541  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
109562200  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha [KO:K04515] [EC:2.7.11.17]
109566133  IL1B; interleukin-1 beta [KO:K04519]
109565502  IL1R1; interleukin-1 receptor type 1 [KO:K04386]
109556715  IL1RAP; interleukin-1 receptor accessory protein isoform X1 [KO:K04723]
109574182  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
109573853  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
109577010  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
109577419  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
109561331  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
109560650  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
109553773  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
109555882  NGF; beta-nerve growth factor [KO:K02582]
109556725  NTRK1; high affinity nerve growth factor receptor [KO:K03176] [EC:2.7.10.1]
109567698  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 [KO:K01116] [EC:3.1.4.11]
109572707  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X1 [KO:K05859] [EC:3.1.4.11]
109559805  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
109570415  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
109557823  PIK3CA; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
109574805  PIK3R1; LOW QUALITY PROTEIN: phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
109561418  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
109556345  phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
109576388  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
109567428  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
109556555  TRPM8; transient receptor potential cation channel subfamily M member 8 isoform X1 [KO:K04983]
109564679  PTGER2; prostaglandin E2 receptor EP2 subtype [KO:K04259]
109574951  PTGER4; prostaglandin E2 receptor EP4 subtype [KO:K04261]
109567291  guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas-like [KO:K04632]
109567292  neuroendocrine secretory protein 55 [KO:K04632]
109557525  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
109574822  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
109566330  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
109564199  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
109555842  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
109559159  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
109572478  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
109568647  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
109578364  ADCY9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
109556827  PRKACB; LOW QUALITY PROTEIN: cAMP-dependent protein kinase catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
109561498  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
109571556  TRPV4; transient receptor potential cation channel subfamily V member 4 [KO:K04973]
109564650  F2RL1; proteinase-activated receptor 2 [KO:K04234]
109553149  cytochrome P450 2C31 [KO:K07413] [EC:1.14.14.1]
109553151  cytochrome P450 2C23-like isoform X1 [KO:K07413] [EC:1.14.14.1]
109553148  cytochrome P450 2C31-like [KO:K07413] [EC:1.14.14.1]
109553136  cytochrome P450 2C9-like [KO:K07413] [EC:1.14.14.1]
109579059  cytochrome P450 2C19-like [KO:K07413] [EC:1.14.14.1]
109553186  cytochrome P450 2C18-like [KO:K07413] [EC:1.14.14.1]
109556861  cytochrome P450 2J2-like [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
109556228  cytochrome P450 2J2-like isoform X1 [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
109556325  cytochrome P450 4A25-like [KO:K07425] [EC:1.14.14.80]
109556328  taurochenodeoxycholic 6 alpha-hydroxylase-like isoform X1 [KO:K07425] [EC:1.14.14.80]
109573366  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
109578560  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
109572998  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
109565229  protein kinase C eta type [KO:K18051] [EC:2.7.11.13]
109567889  PRKCQ; protein kinase C theta type [KO:K18052] [EC:2.7.11.13]
109559448  IGF1; insulin-like growth factor I isoform X1 [KO:K05459]
109574348  TRPV2; transient receptor potential cation channel subfamily V member 2 [KO:K04971]
109574452  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
biu00590  Arachidonic acid metabolism
biu04010  MAPK signaling pathway
biu04020  Calcium signaling pathway
KO pathway
ko04750   
LinkDB

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