KEGG   PATHWAY: mlx04750
Entry
mlx04750                    Pathway                                
Name
Inflammatory mediator regulation of TRP channels - Mirounga leonina (Southern elephant seal)
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
mlx04750  Inflammatory mediator regulation of TRP channels
mlx04750

Other DBs
GO: 0019233
Organism
Mirounga leonina (Southern elephant seal) [GN:mlx]
Gene
118000407  KNG1; kininogen-1 isoform X1 [KO:K03898]
118002481  BDKRB1; LOW QUALITY PROTEIN: B1 bradykinin receptor [KO:K03915]
118002013  BDKRB2; B2 bradykinin receptor isoform X1 [KO:K03916]
118009426  HTR2A; 5-hydroxytryptamine receptor 2A [KO:K04157]
118011377  HTR2C; 5-hydroxytryptamine receptor 2C isoform X1 [KO:K04157]
118011956  HTR2B; 5-hydroxytryptamine receptor 2B isoform X1 [KO:K04157]
118006038  HRH1; histamine H1 receptor isoform X1 [KO:K04149]
118004321  P2RY2; P2Y purinoceptor 2 [KO:K04269]
118026266  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
118003270  PLA2G4E; cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]
118003295  PLA2G4F; cytosolic phospholipase A2 zeta [KO:K16342] [EC:3.1.1.4]
118003418  cytosolic phospholipase A2 beta isoform X1 [KO:K16342] [EC:3.1.1.4]
118003546  PLA2G4D; cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
118014408  PLA2G4A; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
117998687  PLA2G6; 85/88 kDa calcium-independent phospholipase A2 isoform X1 [KO:K16343] [EC:3.1.1.4]
117999978  ALOX12; polyunsaturated fatty acid lipoxygenase ALOX12 isoform X1 [KO:K00458] [EC:1.13.11.31]
117999898  LOW QUALITY PROTEIN: polyunsaturated fatty acid (12S)/(13S)-lipoxygenase, epidermal-type-like [KO:K00458] [EC:1.13.11.31]
118015997  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
118003092  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
118011244  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
118011247  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
118005236  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
118025560  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
118001326  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
118008176  PRKCE; protein kinase C epsilon type [KO:K18050] [EC:2.7.11.13]
118007723  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
118016125  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
118018468  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
118015385  TRPA1; transient receptor potential cation channel subfamily A member 1 [KO:K04984]
118025171  TRPV1; transient receptor potential cation channel subfamily V member 1 isoform X1 [KO:K05222]
118008860  ASIC1; acid-sensing ion channel 1 isoform X1 [KO:K04829]
118025123  ASIC2; acid-sensing ion channel 2 [KO:K04828]
118026781  ASIC3; acid-sensing ion channel 3 isoform X1 [KO:K04830]
118012015  ASIC4; acid-sensing ion channel 4 [KO:K04831]
118022430  ASIC5; acid-sensing ion channel 5 [KO:K04832]
118008161  CALM2; calmodulin-2 [KO:K02183]
118016596  calmodulin-1-like [KO:K02183]
118002566  CALM1; calmodulin-1 [KO:K02183]
118003137  CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183]
118012486  calmodulin-like [KO:K02183]
118019658  CALML6; calmodulin-like protein 6 [KO:K02183]
117998176  CALM3; calmodulin-3 [KO:K02183]
118020691  calmodulin-1-like [KO:K02183]
118021620  CALML3; calmodulin-like protein 3 [KO:K02183]
118021903  calmodulin-like [KO:K02183]
118024497  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta [KO:K04515] [EC:2.7.11.17]
118027107  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
118006598  calcium/calmodulin-dependent protein kinase type II subunit alpha [KO:K04515] [EC:2.7.11.17]
118006728  calcium/calmodulin-dependent protein kinase type II subunit alpha [KO:K04515] [EC:2.7.11.17]
118021697  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
118007867  IL1B; interleukin-1 beta [KO:K04519]
118008270  IL1R1; LOW QUALITY PROTEIN: interleukin-1 receptor type 1 [KO:K04386]
118006943  IL1RAP; interleukin-1 receptor accessory protein isoform X1 [KO:K04723]
118000167  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
118024329  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
118001095  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
118001265  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
117997742  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
117997743  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
118022776  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
118010368  mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
118026506  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
118000488  NGF; beta-nerve growth factor [KO:K02582]
118013921  NTRK1; high affinity nerve growth factor receptor [KO:K03176] [EC:2.7.10.1]
118011488  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
118023528  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
118004424  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
118020028  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
118006556  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
118016863  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
118019468  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
118006042  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
118005176  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
118011463  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
118011717  TRPM8; transient receptor potential cation channel subfamily M member 8 [KO:K04983]
118002170  PTGER2; prostaglandin E2 receptor EP2 subtype [KO:K04259]
118006386  prostaglandin E2 receptor EP4 subtype [KO:K04261]
118006517  prostaglandin E2 receptor EP4 subtype [KO:K04261]
118023087  LOW QUALITY PROTEIN: guanine nucleotide-binding protein G(s) subunit alpha-like [KO:K04632]
118024008  neuroendocrine secretory protein 55 [KO:K04632]
118024010  guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
118024512  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
118006264  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
118007652  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
118003693  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
118007016  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
118008901  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
118023800  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
118015219  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
118021775  ADCY9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
118005070  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
118019227  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
118018328  TRPV4; transient receptor potential cation channel subfamily V member 4 [KO:K04973]
118016489  F2RL1; proteinase-activated receptor 2 [KO:K04234]
118024006  cytochrome P450 2C41 [KO:K07413] [EC:1.14.14.1]
118024011  cytochrome P450 2C21 isoform X1 [KO:K07413] [EC:1.14.14.1]
118020215  cytochrome P450 2J2 [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
118024347  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
117999123  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
117997993  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
118002020  PRKCH; protein kinase C eta type isoform X1 [KO:K18051] [EC:2.7.11.13]
118021606  PRKCQ; protein kinase C theta type [KO:K18052] [EC:2.7.11.13]
117998812  IGF1; insulin-like growth factor I isoform X1 [KO:K05459]
118000105  TRPV2; transient receptor potential cation channel subfamily V member 2 isoform X1 [KO:K04971]
118025175  TRPV3; transient receptor potential cation channel subfamily V member 3 [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
PMID:15820689
  Authors
Wang H, Woolf CJ
  Title
Pain TRPs.
  Journal
Neuron 46:9-12 (2005)
DOI:10.1016/j.neuron.2005.03.011
Reference
PMID:17321113
  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
PMID:18427980
  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
PMID:24099085
  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
PMID:12838328
  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
PMID:16776582
  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
PMID:18615141
  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
PMID:17548207
  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
PMID:16319926
  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
PMID:19074743
  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
PMID:17684094
  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
PMID:21841075
  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
PMID:20932256
  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
PMID:23000387
  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
PMID:17124270
  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
PMID:22470230
  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
mlx00590  Arachidonic acid metabolism
mlx04010  MAPK signaling pathway
mlx04020  Calcium signaling pathway
KO pathway
ko04750   
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