KEGG   PATHWAY: ocu04750
Entry
ocu04750                    Pathway                                
Name
Inflammatory mediator regulation of TRP channels - Oryctolagus cuniculus (rabbit)
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
ocu04750  Inflammatory mediator regulation of TRP channels
ocu04750

Other DBs
GO: 0019233
Organism
Oryctolagus cuniculus (rabbit) [GN:ocu]
Gene
100008668  IGF1; insulin-like growth factor I precursor [KO:K05459]
100008748  PLA2G4A; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
100008815  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
100008904  [KO:K04632]
100008926  TRPV1; transient receptor potential cation channel subfamily V member 1 [KO:K05222]
100008939  [KO:K04960]
100008961  PLA2G6; 85/88 kDa calcium-independent phospholipase A2 [KO:K16343] [EC:3.1.1.4]
100008966  [KO:K06068] [EC:2.7.11.13]
100008990  IL1B; interleukin-1 beta precursor [KO:K04519]
100009081  PTGER4; prostaglandin E2 receptor EP4 subtype [KO:K04261]
100009102  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
100009103  PRKCE; protein kinase C epsilon type [KO:K18050] [EC:2.7.11.13]
100009198  BDKRB1; B1 bradykinin receptor [KO:K03915]
100009201  [KO:K08042] [EC:4.6.1.1]
100009298  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
100009315  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
100009369  PTGER2; prostaglandin E2 receptor EP2 subtype [KO:K04259]
100009461  [KO:K04157]
100009505  [KO:K04958]
100009587  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
100037719  PRKCB; protein kinase C beta type isoform I [KO:K19662] [EC:2.7.11.13]
100037720  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
100101556  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma [KO:K04515] [EC:2.7.11.17]
100101557  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta [KO:K04515] [EC:2.7.11.17]
100101602  [KO:K03898]
100216510  ASIC4; acid-sensing ion channel 4 [KO:K04831]
100301544  CYP2J1; cytochrome P450 2J1 [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
100328549  CYP2C5; cytochrome P450 2C5 precursor [KO:K07413] [EC:1.14.14.1]
100328924  CYP2C2; cytochrome P450 2C2 precursor [KO:K07413] [EC:1.14.14.1]
100328933  CYP2C; cytochrome P450 2C3 precursor [KO:K07413] [EC:1.14.14.1]
100328935  CYP2C30; cytochrome P450 2C30 precursor [KO:K07413] [EC:1.14.14.1]
100328936  CYP2C14; cytochrome P450 2C14 precursor [KO:K07413] [EC:1.14.14.1]
100328938  CYP2C16; cytochrome P450 2C16 precursor [KO:K07413] [EC:1.14.14.1]
100337822  [KO:K00922] [EC:2.7.1.153]
100337882  [KO:K08048] [EC:4.6.1.1]
100337999  [KO:K04440] [EC:2.7.11.24]
100338359  [KO:K03916]
100339953  [KO:K04432] [EC:2.7.12.2]
100340139  [KO:K05859] [EC:3.1.4.11]
100340517  [KO:K16342] [EC:3.1.1.4]
100340525  [KO:K00458] [EC:1.13.11.31]
100340719  [KO:K04634]
100340775  [KO:K16342] [EC:3.1.1.4]
100340877  [KO:K08049] [EC:4.6.1.1]
100341033  PLA2G4E; cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]
100341237  [KO:K16342] [EC:3.1.1.4]
100341281  [KO:K04723]
100341337  [KO:K04984]
100341507  [KO:K04515] [EC:2.7.11.17]
100341512  [KO:K05858] [EC:3.1.4.11]
100341599  [KO:K05704] [EC:2.7.10.2]
100341695  [KO:K04441] [EC:2.7.11.24]
100342212  [KO:K04345] [EC:2.7.11.11]
100342451  [KO:K04515] [EC:2.7.11.17]
100342664  [KO:K04440] [EC:2.7.11.24]
100343085  [KO:K04828]
100343392  [KO:K04157]
100343600  [KO:K04157]
100343958  [KO:K08043] [EC:4.6.1.1]
100344161  [KO:K04441] [EC:2.7.11.24]
100344184  [KO:K18051] [EC:2.7.11.13]
100345181  [KO:K00922] [EC:2.7.1.153]
100345193  [KO:K07413] [EC:1.14.14.1]
100345250  [KO:K02649]
100345526  [KO:K02183]
100346305  [KO:K07413] [EC:1.14.14.1]
100346323  [KO:K04632]
100346742  [KO:K08044] [EC:4.6.1.1]
100346743  CYP2C1; cytochrome P450 2C1 isoform X1 [KO:K07413] [EC:1.14.14.1]
100346929  [KO:K04440] [EC:2.7.11.24]
100347856  [KO:K02183]
100348650  [KO:K04149]
100348663  [KO:K00922] [EC:2.7.1.153]
100348672  [KO:K05858] [EC:3.1.4.11]
100349436  CYP2C4; cytochrome P450 2C4 precursor [KO:K07413] [EC:1.14.14.1]
100349595  [KO:K04832]
100349958  [KO:K01116] [EC:3.1.4.11]
100350107  [KO:K02183]
100350303  [KO:K04234]
100350395  [KO:K05858] [EC:3.1.4.11]
100350503  [KO:K04830]
100350614  [KO:K04441] [EC:2.7.11.24]
100351058  [KO:K04973]
100351107  [KO:K04983]
100352392  CALM2; calmodulin [KO:K02183]
100352905  [KO:K04386]
100353054  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
100353460  [KO:K07413] [EC:1.14.14.1]
100354292  [KO:K03176] [EC:2.7.10.1]
100354812  [KO:K04971]
100354905  [KO:K02183]
100354934  [KO:K08046] [EC:4.6.1.1]
100355230  [KO:K04433] [EC:2.7.12.2]
100355724  [KO:K04972]
100355858  [KO:K04829]
100356806  [KO:K04959]
100357357  [KO:K08047] [EC:4.6.1.1]
100357841  [KO:K02649]
100533118  PLA2G4B; cytosolic phospholipase A2 beta [KO:K16342] [EC:3.1.1.4]
103344944  [KO:K04269]
103345165  [KO:K02183]
103346035  [KO:K04441] [EC:2.7.11.24]
103347035  [KO:K08041] [EC:4.6.1.1]
103347536  [KO:K05858] [EC:3.1.4.11]
103350089  [KO:K02582]
103350889  [KO:K18052] [EC:2.7.11.13]
103351405  [KO:K07413] [EC:1.14.14.1]
127488311  [KO:K04830]
127490931  [KO:K16343] [EC:3.1.1.4]
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
ocu00590  Arachidonic acid metabolism
ocu04010  MAPK signaling pathway
ocu04020  Calcium signaling pathway
KO pathway
ko04750   

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