KEGG   PATHWAY: mmu04750
Entry
mmu04750                    Pathway                                
Name
Inflammatory mediator regulation of TRP channels - Mus musculus (house 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
mmu04750  Inflammatory mediator regulation of TRP channels
mmu04750

Other DBs
GO: 0019233
Organism
Mus musculus (house mouse) [GN:mmu]
Gene
16644  Kng1; kininogen 1 [KO:K03898]
385643  Kng2; kininogen 2 [KO:K03898]
12061  Bdkrb1; bradykinin receptor, beta 1 [KO:K03915]
12062  Bdkrb2; bradykinin receptor, beta 2 [KO:K03916]
15558  Htr2a; 5-hydroxytryptamine (serotonin) receptor 2A [KO:K04157]
15559  Htr2b; 5-hydroxytryptamine (serotonin) receptor 2B [KO:K04157]
15560  Htr2c; 5-hydroxytryptamine (serotonin) receptor 2C [KO:K04157]
15465  Hrh1; histamine receptor H1 [KO:K04149]
18442  P2ry2; purinergic receptor P2Y, G-protein coupled 2 [KO:K04269]
14682  Gnaq; guanine nucleotide binding protein, alpha q polypeptide [KO:K04634]
329502  Pla2g4e; phospholipase A2, group IVE [KO:K16342] [EC:3.1.1.4]
18783  Pla2g4a; phospholipase A2, group IVA (cytosolic, calcium-dependent) [KO:K16342] [EC:3.1.1.4]
211429  Pla2g4b; phospholipase A2, group IVB (cytosolic) [KO:K16342] [EC:3.1.1.4]
232889  Pla2g4c; phospholipase A2, group IVC (cytosolic, calcium-independent) [KO:K16342] [EC:3.1.1.4]
78390  Pla2g4d; phospholipase A2, group IVD [KO:K16342] [EC:3.1.1.4]
271844  Pla2g4f; phospholipase A2, group IVF [KO:K16342] [EC:3.1.1.4]
53357  Pla2g6; phospholipase A2, group VI [KO:K16343] [EC:3.1.1.4]
11684  Alox12; arachidonate 12-lipoxygenase [KO:K00458] [EC:1.13.11.31]
11685  Alox12e; arachidonate lipoxygenase, epidermal [KO:K00458] [EC:1.13.11.31]
18795  Plcb1; phospholipase C, beta 1 [KO:K05858] [EC:3.1.4.11]
18797  Plcb3; phospholipase C, beta 3 [KO:K05858] [EC:3.1.4.11]
18798  Plcb4; phospholipase C, beta 4 [KO:K05858] [EC:3.1.4.11]
18796  Plcb2; phospholipase C, beta 2 [KO:K05858] [EC:3.1.4.11]
16438  Itpr1; inositol 1,4,5-trisphosphate receptor 1 [KO:K04958]
16439  Itpr2; inositol 1,4,5-triphosphate receptor 2 [KO:K04959]
16440  Itpr3; inositol 1,4,5-triphosphate receptor 3 [KO:K04960]
18754  Prkce; protein kinase C, epsilon [KO:K18050] [EC:2.7.11.13]
19045  Ppp1ca; protein phosphatase 1 catalytic subunit alpha [KO:K06269] [EC:3.1.3.16]
19046  Ppp1cb; protein phosphatase 1 catalytic subunit beta [KO:K06269] [EC:3.1.3.16]
19047  Ppp1cc; protein phosphatase 1 catalytic subunit gamma [KO:K06269] [EC:3.1.3.16]
434233  Ppp1ccb; protein phosphatase 1 catalytic subunit gamma B [KO:K06269] [EC:3.1.3.16]
277328  Trpa1; transient receptor potential cation channel, subfamily A, member 1 [KO:K04984]
193034  Trpv1; transient receptor potential cation channel, subfamily V, member 1 [KO:K05222]
11419  Asic1; acid-sensing ion channel 1 [KO:K04829]
11418  Asic2; acid-sensing ion channel 2 [KO:K04828]
171209  Asic3; acid-sensing ion channel 3 [KO:K04830]
241118  Asic4; acid-sensing ion channel family member 4 [KO:K04831]
58170  Asic5; acid-sensing ion channel family member 5 [KO:K04832]
12313  Calm1; calmodulin 1 [KO:K02183]
80796  Calm4; calmodulin 4 [KO:K02183]
12315  Calm3; calmodulin 3 [KO:K02183]
12314  Calm2; calmodulin 2 [KO:K02183]
70405  Calml3; calmodulin-like 3 [KO:K02183]
494124  Calm5; calmodulin 5 [KO:K02183]
75600  Calml4; calmodulin-like 4 [KO:K02183]
108058  Camk2d; calcium/calmodulin-dependent protein kinase II, delta [KO:K04515] [EC:2.7.11.17]
12325  Camk2g; calcium/calmodulin-dependent protein kinase II gamma [KO:K04515] [EC:2.7.11.17]
12323  Camk2b; calcium/calmodulin-dependent protein kinase II, beta [KO:K04515] [EC:2.7.11.17]
12322  Camk2a; calcium/calmodulin-dependent protein kinase II alpha [KO:K04515] [EC:2.7.11.17]
16176  Il1b; interleukin 1 beta [KO:K04519]
16177  Il1r1; interleukin 1 receptor, type I [KO:K04386]
16180  Il1rap; interleukin 1 receptor accessory protein [KO:K04723]
26397  Map2k3; mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
26399  Map2k6; mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
26416  Mapk14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
19094  Mapk11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
29857  Mapk12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
26415  Mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
26419  Mapk8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
26420  Mapk9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
26414  Mapk10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
18048  Klk1b4; kallikrein 1-related pepidase b4 [KO:K05451]
18049  Ngf; nerve growth factor [KO:K02582]
18211  Ntrk1; neurotrophic tyrosine kinase, receptor, type 1 [KO:K03176] [EC:2.7.10.1]
18803  Plcg1; phospholipase C, gamma 1 [KO:K01116] [EC:3.1.4.11]
234779  Plcg2; phospholipase C, gamma 2 [KO:K05859] [EC:3.1.4.11]
18706  Pik3ca; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
18707  Pik3cd; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
74769  Pik3cb; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
18709  Pik3r2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
18708  Pik3r1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
18710  Pik3r3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
18753  Prkcd; protein kinase C, delta [KO:K06068] [EC:2.7.11.13]
20779  Src; Rous sarcoma oncogene [KO:K05704] [EC:2.7.10.2]
171382  Trpm8; transient receptor potential cation channel, subfamily M, member 8 [KO:K04983]
19217  Ptger2; prostaglandin E receptor 2 (subtype EP2) [KO:K04259]
19219  Ptger4; prostaglandin E receptor 4 (subtype EP4) [KO:K04261]
14683  Gnas; GNAS complex locus [KO:K04632]
432530  Adcy1; adenylate cyclase 1 [KO:K08041] [EC:4.6.1.1]
210044  Adcy2; adenylate cyclase 2 [KO:K08042] [EC:4.6.1.1]
104111  Adcy3; adenylate cyclase 3 [KO:K08043] [EC:4.6.1.1]
104110  Adcy4; adenylate cyclase 4 [KO:K08044] [EC:4.6.1.1]
224129  Adcy5; adenylate cyclase 5 [KO:K08045] [EC:4.6.1.1]
11512  Adcy6; adenylate cyclase 6 [KO:K08046] [EC:4.6.1.1]
11513  Adcy7; adenylate cyclase 7 [KO:K08047] [EC:4.6.1.1]
11514  Adcy8; adenylate cyclase 8 [KO:K08048] [EC:4.6.1.1]
11515  Adcy9; adenylate cyclase 9 [KO:K08049] [EC:4.6.1.1]
18747  Prkaca; protein kinase, cAMP dependent, catalytic, alpha [KO:K04345] [EC:2.7.11.11]
18749  Prkacb; protein kinase, cAMP dependent, catalytic, beta [KO:K04345] [EC:2.7.11.11]
63873  Trpv4; transient receptor potential cation channel, subfamily V, member 4 [KO:K04973]
14063  F2rl1; F2R like trypsin receptor 1 [KO:K04234]
13097  Cyp2c38; cytochrome P450, family 2, subfamily c, polypeptide 38 [KO:K07413] [EC:1.14.14.1]
13098  Cyp2c39; cytochrome P450, family 2, subfamily c, polypeptide 39 [KO:K07413] [EC:1.14.14.1]
13099  Cyp2c40; cytochrome P450, family 2, subfamily c, polypeptide 40 [KO:K07413] [EC:1.14.14.1]
226143  Cyp2c23; cytochrome P450, family 2, subfamily c, polypeptide 23 [KO:K07413] [EC:1.14.14.1]
13095  Cyp2c29; cytochrome P450, family 2, subfamily c, polypeptide 29 [KO:K07413] [EC:1.14.14.1]
226105  Cyp2c70; cytochrome P450, family 2, subfamily c, polypeptide 70 [KO:K07413] [EC:1.14.14.1]
13096  Cyp2c37; cytochrome P450, family 2. subfamily c, polypeptide 37 [KO:K07413] [EC:1.14.14.1]
72082  Cyp2c55; cytochrome P450, family 2, subfamily c, polypeptide 55 [KO:K07413] [EC:1.14.14.1]
72303  Cyp2c65; cytochrome P450, family 2, subfamily c, polypeptide 65 [KO:K07413] [EC:1.14.14.1]
69888  Cyp2c66; cytochrome P450, family 2, subfamily c, polypeptide 66 [KO:K07413] [EC:1.14.14.1]
107141  Cyp2c50; cytochrome P450, family 2, subfamily c, polypeptide 50 [KO:K07413] [EC:1.14.14.1]
404195  Cyp2c54; cytochrome P450, family 2, subfamily c, polypeptide 54 [KO:K07413] [EC:1.14.14.1]
433247  Cyp2c68; cytochrome P450, family 2, subfamily c, polypeptide 68 [KO:K07413] [EC:1.14.14.1]
100043108  Cyp2c69; cytochrome P450, family 2, subfamily c, polypeptide 69 [KO:K07413] [EC:1.14.14.1]
545288  Cyp2c67; cytochrome P450, family 2, subfamily c, polypeptide 67 [KO:K07413] [EC:1.14.14.1]
665095  Cyp2j8; cytochrome P450, family 2, subfamily j, polypeptide 8 [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
230459  Cyp2j13; cytochrome P450, family 2, subfamily j, polypeptide 13 [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
100066  Cyp2j11; cytochrome P450, family 2, subfamily j, polypeptide 11 [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
74519  Cyp2j9; cytochrome P450, family 2, subfamily j, polypeptide 9 [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
13109  Cyp2j5; cytochrome P450, family 2, subfamily j, polypeptide 5 [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
242546  Cyp2j12; cytochrome P450, family 2, subfamily j, polypeptide 12 [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
13110  Cyp2j6; cytochrome P450, family 2, subfamily j, polypeptide 6 [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
546837  Cyp2j7; cytochrome P450, family 2, subfamily j, polypeptide 7 [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
13118  Cyp4a12b; cytochrome P450, family 4, subfamily a, polypeptide 12B [KO:K07425] [EC:1.14.14.80]
13117  Cyp4a10; cytochrome P450, family 4, subfamily a, polypeptide 10 [KO:K07425] [EC:1.14.14.80]
13119  Cyp4a14; cytochrome P450, family 4, subfamily a, polypeptide 14 [KO:K07425] [EC:1.14.14.80]
435802  Cyp4a30b; cytochrome P450, family 4, subfamily a, polypeptide 30b [KO:K07425] [EC:1.14.14.80]
230639  Cyp4a29; cytochrome P450, family 4, subfamily a, polypeptide 29 [KO:K07425] [EC:1.14.14.80]
666168  Cyp4a31; cytochrome P450, family 4, subfamily a, polypeptide 31 [KO:K07425] [EC:1.14.14.80]
100040843  Cyp4a32; cytochrome P450, family 4, subfamily a, polypeptide 32 [KO:K07425] [EC:1.14.14.80]
277753  Cyp4a12a; cytochrome P450, family 4, subfamily a, polypeptide 12a [KO:K07425] [EC:1.14.14.80]
18750  Prkca; protein kinase C, alpha [KO:K02677] [EC:2.7.11.13]
18751  Prkcb; protein kinase C, beta [KO:K19662] [EC:2.7.11.13]
18752  Prkcg; protein kinase C, gamma [KO:K19663] [EC:2.7.11.13]
18755  Prkch; protein kinase C, eta [KO:K18051] [EC:2.7.11.13]
18761  Prkcq; protein kinase C, theta [KO:K18052] [EC:2.7.11.13]
16000  Igf1; insulin-like growth factor 1 [KO:K05459]
22368  Trpv2; transient receptor potential cation channel, subfamily V, member 2 [KO:K04971]
246788  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
mmu00590  Arachidonic acid metabolism
mmu04010  MAPK signaling pathway
mmu04020  Calcium signaling pathway
KO pathway
ko04750   
LinkDB

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