KEGG   PATHWAY: hsa04750Help
Entry
hsa04750                    Pathway                                

Name
Inflammatory mediator regulation of TRP channels - Homo sapiens (human)
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
BRITE hierarchy
Pathway map
Inflammatory mediator regulation of TRP channels
hsa04750

All organismsOrtholog table
Disease
H01391  
Familial episodic pain syndrome (FEPS)
Other DBs
BSID: 
GO: 
Organism
Homo sapiens (human) [GN:hsa]
Gene
623  
BDKRB1; bradykinin receptor B1 [KO:K03915]
624  
BDKRB2; bradykinin receptor B2 [KO:K03916]
3356  
HTR2A; 5-hydroxytryptamine (serotonin) receptor 2A, G protein-coupled [KO:K04157]
3357  
HTR2B; 5-hydroxytryptamine (serotonin) receptor 2B, G protein-coupled [KO:K04157]
3358  
HTR2C; 5-hydroxytryptamine (serotonin) receptor 2C, G protein-coupled [KO:K04157]
3269  
HRH1; histamine receptor H1 [KO:K04149]
5029  
P2RY2; purinergic receptor P2Y, G-protein coupled, 2 [KO:K04269]
2776  
GNAQ; guanine nucleotide binding protein (G protein), q polypeptide [KO:K04634]
123745  
PLA2G4E; phospholipase A2, group IVE [KO:K16342] [EC:3.1.1.4]
5321  
PLA2G4A; phospholipase A2, group IVA (cytosolic, calcium-dependent) [KO:K16342] [EC:3.1.1.4]
8681  
JMJD7-PLA2G4B; JMJD7-PLA2G4B readthrough [KO:K16342] [EC:3.1.1.4]
PLA2G4B; phospholipase A2, group IVB (cytosolic) [KO:K16342] [EC:3.1.1.4]
8605  
PLA2G4C; phospholipase A2, group IVC (cytosolic, calcium-independent) [KO:K16342] [EC:3.1.1.4]
283748  
PLA2G4D; phospholipase A2, group IVD (cytosolic) [KO:K16342] [EC:3.1.1.4]
255189  
PLA2G4F; phospholipase A2, group IVF [KO:K16342] [EC:3.1.1.4]
8398  
PLA2G6; phospholipase A2, group VI (cytosolic, calcium-independent) [KO:K16343] [EC:3.1.1.4]
239  
ALOX12; arachidonate 12-lipoxygenase [KO:K00458] [EC:1.13.11.31]
23236  
PLCB1; phospholipase C, beta 1 (phosphoinositide-specific) [KO:K05858] [EC:3.1.4.11]
5330  
PLCB2; phospholipase C, beta 2 [KO:K05858] [EC:3.1.4.11]
5331  
PLCB3; phospholipase C, beta 3 (phosphatidylinositol-specific) [KO:K05858] [EC:3.1.4.11]
5332  
PLCB4; phospholipase C, beta 4 [KO:K05858] [EC:3.1.4.11]
3708  
ITPR1; inositol 1,4,5-trisphosphate receptor, type 1 [KO:K04958]
3709  
ITPR2; inositol 1,4,5-trisphosphate receptor, type 2 [KO:K04959]
3710  
ITPR3; inositol 1,4,5-trisphosphate receptor, type 3 [KO:K04960]
5581  
PRKCE; protein kinase C, epsilon [KO:K18050] [EC:2.7.11.13]
5499  
PPP1CA; protein phosphatase 1, catalytic subunit, alpha isozyme [KO:K06269] [EC:3.1.3.16]
5500  
PPP1CB; protein phosphatase 1, catalytic subunit, beta isozyme [KO:K06269] [EC:3.1.3.16]
5501  
PPP1CC; protein phosphatase 1, catalytic subunit, gamma isozyme [KO:K06269] [EC:3.1.3.16]
8989  
TRPA1; transient receptor potential cation channel, subfamily A, member 1 [KO:K04984]
7442  
TRPV1; transient receptor potential cation channel, subfamily V, member 1 [KO:K05222]
41  
ASIC1; acid-sensing (proton-gated) ion channel 1 [KO:K04829]
40  
ASIC2; acid-sensing (proton-gated) ion channel 2 [KO:K04828]
9311  
ASIC3; acid-sensing (proton-gated) ion channel 3 [KO:K04830]
55515  
ASIC4; acid-sensing (proton-gated) ion channel family member 4 [KO:K04831]
51802  
ASIC5; acid-sensing (proton-gated) ion channel family member 5 [KO:K04832]
810  
CALML3; calmodulin-like 3 [KO:K02183]
805  
CALM2; calmodulin 2 (phosphorylase kinase, delta) [KO:K02183]
808  
CALM3; calmodulin 3 (phosphorylase kinase, delta) [KO:K02183]
801  
CALM1; calmodulin 1 (phosphorylase kinase, delta) [KO:K02183]
163688  
CALML6; calmodulin-like 6 [KO:K02183]
51806  
CALML5; calmodulin-like 5 [KO:K02183]
815  
CAMK2A; calcium/calmodulin-dependent protein kinase II alpha [KO:K04515] [EC:2.7.11.17]
817  
CAMK2D; calcium/calmodulin-dependent protein kinase II delta [KO:K04515] [EC:2.7.11.17]
816  
CAMK2B; calcium/calmodulin-dependent protein kinase II beta [KO:K04515] [EC:2.7.11.17]
818  
CAMK2G; calcium/calmodulin-dependent protein kinase II gamma [KO:K04515] [EC:2.7.11.17]
3553  
IL1B; interleukin 1, beta [KO:K04519]
3554  
IL1R1; interleukin 1 receptor, type I [KO:K04386]
3556  
IL1RAP; interleukin 1 receptor accessory protein [KO:K04723]
5606  
MAP2K3; mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
5608  
MAP2K6; mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
5600  
MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
6300  
MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
5603  
MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
1432  
MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
5599  
MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
5602  
MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
5601  
MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
4803  
NGF; nerve growth factor (beta polypeptide) [KO:K02582]
4914  
NTRK1; neurotrophic tyrosine kinase, receptor, type 1 [KO:K03176] [EC:2.7.10.1]
5335  
PLCG1; phospholipase C, gamma 1 [KO:K01116] [EC:3.1.4.11]
5336  
PLCG2; phospholipase C, gamma 2 (phosphatidylinositol-specific) [KO:K05859] [EC:3.1.4.11]
5290  
PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
5293  
PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
5291  
PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
5294  
PIK3CG; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit gamma [KO:K00922] [EC:2.7.1.153]
5295  
PIK3R1; phosphoinositide-3-kinase, regulatory subunit 1 (alpha) [KO:K02649]
23533  
PIK3R5; phosphoinositide-3-kinase, regulatory subunit 5 [KO:K02649]
5296  
PIK3R2; phosphoinositide-3-kinase, regulatory subunit 2 (beta) [KO:K02649]
8503  
PIK3R3; phosphoinositide-3-kinase, regulatory subunit 3 (gamma) [KO:K02649]
5580  
PRKCD; protein kinase C, delta [KO:K06068] [EC:2.7.11.13]
6714  
SRC; SRC proto-oncogene, non-receptor tyrosine kinase [KO:K05704] [EC:2.7.10.2]
79054  
TRPM8; transient receptor potential cation channel, subfamily M, member 8 [KO:K04983]
5732  
PTGER2; prostaglandin E receptor 2 (subtype EP2), 53kDa [KO:K04259]
5734  
PTGER4; prostaglandin E receptor 4 (subtype EP4) [KO:K04261]
2778  
GNAS; GNAS complex locus [KO:K04632]
107  
ADCY1; adenylate cyclase 1 (brain) [KO:K08041] [EC:4.6.1.1]
108  
ADCY2; adenylate cyclase 2 (brain) [KO:K08042] [EC:4.6.1.1]
109  
ADCY3; adenylate cyclase 3 [KO:K08043] [EC:4.6.1.1]
196883  
ADCY4; adenylate cyclase 4 [KO:K08044] [EC:4.6.1.1]
111  
ADCY5; adenylate cyclase 5 [KO:K08045] [EC:4.6.1.1]
112  
ADCY6; adenylate cyclase 6 [KO:K08046] [EC:4.6.1.1]
113  
ADCY7; adenylate cyclase 7 [KO:K08047] [EC:4.6.1.1]
114  
ADCY8; adenylate cyclase 8 (brain) [KO:K08048] [EC:4.6.1.1]
115  
ADCY9; adenylate cyclase 9 [KO:K08049] [EC:4.6.1.1]
5566  
PRKACA; protein kinase, cAMP-dependent, catalytic, alpha [KO:K04345] [EC:2.7.11.11]
5567  
PRKACB; protein kinase, cAMP-dependent, catalytic, beta [KO:K04345] [EC:2.7.11.11]
5568  
PRKACG; protein kinase, cAMP-dependent, catalytic, gamma [KO:K04345] [EC:2.7.11.11]
5613  
PRKX; protein kinase, X-linked [KO:K04345] [EC:2.7.11.11]
59341  
TRPV4; transient receptor potential cation channel, subfamily V, member 4 [KO:K04973]
2150  
F2RL1; coagulation factor II (thrombin) receptor-like 1 [KO:K04234]
1573  
CYP2J2; cytochrome P450, family 2, subfamily J, polypeptide 2 [KO:K07418] [EC:1.14.14.1]
5578  
PRKCA; protein kinase C, alpha [KO:K02677] [EC:2.7.11.13]
5579  
PRKCB; protein kinase C, beta [KO:K02677] [EC:2.7.11.13]
5582  
PRKCG; protein kinase C, gamma [KO:K02677] [EC:2.7.11.13]
5583  
PRKCH; protein kinase C, eta [KO:K18051] [EC:2.7.11.13]
5588  
PRKCQ; protein kinase C, theta [KO:K18052] [EC:2.7.11.13]
3479  
IGF1; insulin-like growth factor 1 (somatomedin C) [KO:K05459]
51393  
TRPV2; transient receptor potential cation channel, subfamily V, member 2 [KO:K04971]
162514  
TRPV3; transient receptor potential cation channel, subfamily V, member 3 [KO:K04972]
Compound
C00002  
ATP
C00076  
Calcium cation
C00080  
H+
C00165  
Diacylglycerol
C00219  
Arachidonate
C00306  
Bradykinin
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)-Eicosapentaenoic acid
C12271  
N-Arachidonyl dopamine
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)
Reference
  Authors
Levine JD, Alessandri-Haber N
  Title
TRP channels: targets for the relief of pain.
  Journal
Biochim Biophys Acta 1772:989-1003 (2007)
Reference
  Authors
Cheng JK, Ji RR
  Title
Intracellular signaling in primary sensory neurons and persistent pain.
  Journal
Neurochem Res 33:1970-8 (2008)
Reference
  Authors
Julius D
  Title
TRP channels and pain.
  Journal
Annu Rev Cell Dev Biol 29:355-84 (2013)
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)
Reference
  Authors
Dhaka A, Viswanath V, Patapoutian A
  Title
Trp ion channels and temperature sensation.
  Journal
Annu Rev Neurosci 29:135-61 (2006)
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)
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)
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)
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)
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)
Reference
  Authors
Latorre R, Brauchi S, Madrid R, Orio P
  Title
A cool channel in cold transduction.
  Journal
Physiology (Bethesda) 26:273-85 (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)
Reference
  Authors
Loyd DR, Henry MA, Hargreaves KM
  Title
Serotonergic neuromodulation of peripheral nociceptors.
  Journal
Semin Cell Dev Biol 24:51-7 (2013)
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)
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)
KO pathway
 

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