KEGG   PATHWAY: mpah04750
Entry
mpah04750                   Pathway                                
Name
Inflammatory mediator regulation of TRP channels - Mus pahari (shrew mouse)
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
mpah04750  Inflammatory mediator regulation of TRP channels
mpah04750

Other DBs
GO: 0019233
Organism
Mus pahari (shrew mouse) [GN:mpah]
Gene
110312794  Ppp1cc; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
110313621  Htr2c; 5-hydroxytryptamine receptor 2C [KO:K04157]
110315778  [KO:K07425] [EC:1.14.14.80]
110315988  Asic3; acid-sensing ion channel 3 isoform X1 [KO:K04830]
110316991  Hrh1; histamine H1 receptor [KO:K04149]
110317198  Ppp1ca; serine/threonine-protein phosphatase PP1-alpha catalytic subunit isoform X1 [KO:K06269] [EC:3.1.3.16]
110317210  Itpr1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
110317251  Itpr2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
110317699  [KO:K04632]
110317700  [KO:K04632]
110317793  Src; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
110317815  Plcb4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
110317835  Pla2g4b; cytosolic phospholipase A2 beta [KO:K16342] [EC:3.1.1.4]
110318415  Plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
110318542  Pla2g4f; cytosolic phospholipase A2 zeta isoform X1 [KO:K16342] [EC:3.1.1.4]
110318652  [KO:K07413] [EC:1.14.14.1]
110318953  Pla2g4d; cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
110319321  Il1b; interleukin-1 beta isoform X1 [KO:K04519]
110319432  Pla2g4e; cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]
110319646  Plcb1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
110319649  Plcg1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
110319750  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
110319787  Ntrk1; high affinity nerve growth factor receptor isoform X1 [KO:K03176] [EC:2.7.10.1]
110320075  Prkcb; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
110320585  Ngf; beta-nerve growth factor [KO:K02582]
110320932  Camk2d; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
110320947  Asic5; acid-sensing ion channel 5 [KO:K04832]
110320995  Prkacb; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
110321310  Htr2b; 5-hydroxytryptamine receptor 2B [KO:K04157]
110321382  Pla2g4a; cytosolic phospholipase A2 isoform X1 [KO:K16342] [EC:3.1.1.4]
110321407  Il1r1; interleukin-1 receptor type 1 [KO:K04386]
110321409  [KO:K07413] [EC:1.14.14.1]
110321580  Asic4; LOW QUALITY PROTEIN: acid-sensing ion channel 4 [KO:K04831]
110321587  Trpm8; transient receptor potential cation channel subfamily M member 8 [KO:K04983]
110322859  [KO:K07425] [EC:1.14.14.80]
110322865  Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
110322974  [KO:K07425] [EC:1.14.14.80]
110323111  [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
110323152  [KO:K07425] [EC:1.14.14.80]
110323251  [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
110323340  [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
110323372  [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
110323386  [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
110323448  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
110323498  [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
110323738  [KO:K07413] [EC:1.14.14.1]
110323837  [KO:K07425] [EC:1.14.14.80]
110324176  Prkch; protein kinase C eta type [KO:K18051] [EC:2.7.11.13]
110324261  Calm1; calmodulin [KO:K02183]
110324329  Ppp1cb; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
110324646  Adcy3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
110324855  Bdkrb2; B2 bradykinin receptor isoform X1 [KO:K03916]
110325005  Bdkrb1; B1 bradykinin receptor [KO:K03915]
110325439  Adcy4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
110325466  Mapk8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
110325574  Camk2g; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
110325595  Htr2a; 5-hydroxytryptamine receptor 2A [KO:K04157]
110325898  Ptger2; prostaglandin E2 receptor EP2 subtype [KO:K04259]
110326026  Prkcd; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
110326668  Igf1; insulin-like growth factor I isoform X1 [KO:K05459]
110327251  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
110328293  Calml4; calmodulin-like protein 4 isoform X1 [KO:K02183]
110328764  Adcy2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
110328811  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
110329155  Ptger4; prostaglandin E2 receptor EP4 subtype [KO:K04261]
110329201  F2rl1; proteinase-activated receptor 2 [KO:K04234]
110329393  Adcy5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
110329470  [KO:K07413] [EC:1.14.14.1]
110329561  Il1rap; interleukin-1 receptor accessory protein isoform X1 [KO:K04723]
110329624  Adcy9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
110329894  Kng1; kininogen-1 [KO:K03898]
110330025  [KO:K03898]
110330449  Mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
110330531  P2ry2; P2Y purinoceptor 2 [KO:K04269]
110330584  Adcy1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
110331006  Camk2b; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
110331197  Map2k3; dual specificity mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
110331335  Map2k6; dual specificity mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
110331365  Asic2; acid-sensing ion channel 2 isoform X1 [KO:K04828]
110331792  Alox12; arachidonate 12-lipoxygenase, 12S-type isoform X1 [KO:K00458] [EC:1.13.11.31]
110331811  Trpv3; transient receptor potential cation channel subfamily V member 3 [KO:K04972]
110331953  Trpv1; transient receptor potential cation channel subfamily V member 1 isoform X1 [KO:K05222]
110332037  [KO:K00458] [EC:1.13.11.31]
110332652  Mapk9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
110332714  Prkca; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
110332832  Camk2a; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
110333565  [KO:K07413] [EC:1.14.14.1]
110333780  Prkcq; protein kinase C theta type isoform X1 [KO:K18052] [EC:2.7.11.13]
110334170  Calml3; calmodulin-like protein 3 [KO:K02183]
110334182  [KO:K02183]
110334495  Mapk11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
110334500  Adcy6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
110334612  Adcy8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
110334829  Mapk12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
110334864  Pla2g6; 85/88 kDa calcium-independent phospholipase A2 isoform X1 [KO:K16343] [EC:3.1.1.4]
110334933  Asic1; acid-sensing ion channel 1 isoform X1 [KO:K04829]
110336102  Calm2; calmodulin isoform X1 [KO:K02183]
110336160  Prkce; protein kinase C epsilon type isoform X1 [KO:K18050] [EC:2.7.11.13]
110336366  Prkcg; protein kinase C gamma type isoform X1 [KO:K19663] [EC:2.7.11.13]
110336420  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
110336466  Calm3; calmodulin [KO:K02183]
110336671  Plcb3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
110336949  Pla2g4c; cytosolic phospholipase A2 gamma [KO:K16342] [EC:3.1.1.4]
110336980  [KO:K04634]
110337220  Prkaca; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
110337392  Plcg2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
110337453  Adcy7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
110337896  Mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
110337946  Mapk14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
110338229  Itpr3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
110338816  Trpa1; transient receptor potential cation channel subfamily A member 1 isoform X1 [KO:K04984]
110339055  Trpv4; transient receptor potential cation channel subfamily V member 4 isoform X1 [KO:K04973]
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
mpah00590  Arachidonic acid metabolism
mpah04010  MAPK signaling pathway
mpah04020  Calcium signaling pathway
KO pathway
ko04750   

DBGET integrated database retrieval system