KEGG   PATHWAY: shr04726
Entry
shr04726                    Pathway                                
Name
Serotonergic synapse - Sarcophilus harrisii (Tasmanian devil)
Description
Serotonin (5-Hydroxytryptamine, 5-HT) is a monoamine neurotransmitter that plays important roles in physiological functions such as learning and memory, emotion, sleep, pain, motor function and endocrine secretion, as well as in pathological states including abnormal mood and cognition. Once released from presynaptic axonal terminals, 5-HT binds to receptors, which have been divided into 7 subfamilies on the basis of conserved structures and signaling mechanisms. These families include the ionotropic 5-HT3 receptors and G-protein-coupled 5-HT receptors, the 5-HT1 (Gi /Go -coupled), 5-HT2(Gq-coupled), 5-HT4/6/7 (Gs-coupled) and 5-HT5 receptors. Presynaptically localized 5-HT1B receptors are thought to be the autoreceptors that suppress excess 5-HT release. 5-HT's actions are terminated by transporter- mediated reuptake into neurons, leading to catabolism by monoamine oxidase.
Class
Organismal Systems; Nervous system
Pathway map
shr04726  Serotonergic synapse
shr04726

Other DBs
GO: 0007210
Organism
Sarcophilus harrisii (Tasmanian devil) [GN:shr]
Gene
100915442  TPH1; tryptophan 5-hydroxylase 1 [KO:K00502] [EC:1.14.16.4]
100923184  TPH2; tryptophan 5-hydroxylase 2 isoform X1 [KO:K00502] [EC:1.14.16.4]
100917570  DDC; aromatic-L-amino-acid decarboxylase [KO:K01593] [EC:4.1.1.28 4.1.1.105]
100916325  SLC18A2; synaptic vesicular amine transporter [KO:K08155]
100933876  SLC18A1; chromaffin granule amine transporter [KO:K08155]
100926503  voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
100919750  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
100927554  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F [KO:K04853]
100917433  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
100916548  HTR2A; 5-hydroxytryptamine receptor 2A [KO:K04157]
100925360  HTR2B; 5-hydroxytryptamine receptor 2B [KO:K04157]
100923468  HTR2C; 5-hydroxytryptamine receptor 2C [KO:K04157]
100916183  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha isoform X1 [KO:K04634]
100922938  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
100934049  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
100934311  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
100929015  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
100918532  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X7 [KO:K04958]
100921270  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
100916996  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X2 [KO:K04960]
100913337  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
100924022  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
100935225  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
100934330  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100913231  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
100927268  PLA2G4A; cytosolic phospholipase A2 isoform X1 [KO:K16342] [EC:3.1.1.4]
100913647  PLA2G4E; cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]
100927005  PLA2G4C; cytosolic phospholipase A2 gamma isoform X1 [KO:K16342] [EC:3.1.1.4]
100914602  PLA2G4B; cytosolic phospholipase A2 beta [KO:K16342] [EC:3.1.1.4]
100917893  PLA2G4D; cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
100918158  PLA2G4F; cytosolic phospholipase A2 zeta isoform X1 [KO:K16342] [EC:3.1.1.4]
100919120  cytochrome P450 2C23-like [KO:K07413] [EC:1.14.14.1]
100933766  cytochrome P450 2C42-like [KO:K07413] [EC:1.14.14.1]
100927632  cytochrome P450 2C23-like [KO:K07413] [EC:1.14.14.1]
100928062  cytochrome P450 2C23-like [KO:K07413] [EC:1.14.14.1]
100915447  cytochrome P450 2C19-like [KO:K07413] [EC:1.14.14.1]
100920607  cytochrome P450 2C23-like [KO:K07413] [EC:1.14.14.1]
100918856  cytochrome P450 2C23-like [KO:K07413] [EC:1.14.14.1]
100933015  cytochrome P450 2C23-like [KO:K07413] [EC:1.14.14.1]
100926939  LOW QUALITY PROTEIN: cytochrome P450 2D15 [KO:K07414] [EC:1.14.14.1]
100922468  cytochrome P450 2J3-like isoform X3 [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
100921949  cytochrome P450 2J2 [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
100922742  cytochrome P450 2J2 [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
100922989  cytochrome P450 2J2 [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
100921692  cytochrome P450 2J2 [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
116419008  cytochrome P450 2J2 isoform X1 [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
100922209  cytochrome P450 2J2-like isoform X1 [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
100930522  cytochrome P450 4X1-like isoform X1 [KO:K07428] [EC:1.14.14.1]
100930785  taurochenodeoxycholic 6 alpha-hydroxylase [KO:K07428] [EC:1.14.14.1]
100932471  ALOX5; arachidonate 5-lipoxygenase [KO:K00461] [EC:1.13.11.34]
100933073  arachidonate 12-lipoxygenase, 12S-type isoform X1 [KO:K00458] [EC:1.13.11.31]
100934883  ALOX12B; arachidonate 12-lipoxygenase, 12R-type [KO:K08021] [EC:1.13.11.-]
100921165  ALOX15B; arachidonate 15-lipoxygenase B [KO:K08022] [EC:1.13.11.33 1.13.11.-]
100914094  PTGS1; prostaglandin G/H synthase 1 isoform X1 [KO:K00509] [EC:1.14.99.1]
100926756  PTGS2; prostaglandin G/H synthase 2 [KO:K11987] [EC:1.14.99.1]
100933646  HTR3A; 5-hydroxytryptamine receptor 3A [KO:K04819]
100914027  HTR3B; 5-hydroxytryptamine receptor 3B [KO:K04819]
116423671  5-hydroxytryptamine receptor 3C-like [KO:K04819]
116423488  5-hydroxytryptamine receptor 3C-like [KO:K04819]
100931189  HTR4; 5-hydroxytryptamine receptor 4 [KO:K04160]
105750230  HTR6; 5-hydroxytryptamine receptor 6 [KO:K04162]
100923811  HTR7; 5-hydroxytryptamine receptor 7 [KO:K04163]
100930666  GNAS; guanine nucleotide-binding protein G(s) subunit alpha [KO:K04632]
100929360  cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
100915481  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
100934183  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X2 [KO:K04345] [EC:2.7.11.11]
100913731  cAMP-dependent protein kinase catalytic subunit alpha-like [KO:K04345] [EC:2.7.11.11]
100931280  KCNN2; small conductance calcium-activated potassium channel protein 2 isoform X2 [KO:K04943]
100920918  KCND2; potassium voltage-gated channel subfamily D member 2 isoform X1 [KO:K04892]
100913374  GABRB2; gamma-aminobutyric acid receptor subunit beta-2 isoform X1 [KO:K05181]
100933247  GABRB1; gamma-aminobutyric acid receptor subunit beta-1 [KO:K05181]
100915677  GABRB3; gamma-aminobutyric acid receptor subunit beta-3 [KO:K05181]
100925807  RAPGEF3; rap guanine nucleotide exchange factor 3 isoform X1 [KO:K08014]
100932185  APP; amyloid-beta precursor protein isoform X1 [KO:K04520]
100923440  HTR1B; 5-hydroxytryptamine receptor 1B [KO:K04153]
100922195  HTR1A; 5-hydroxytryptamine receptor 1A [KO:K04153]
100922896  HTR1D; 5-hydroxytryptamine receptor 1D isoform X1 [KO:K04153]
100929316  HTR1F; 5-hydroxytryptamine receptor 1F [KO:K04153]
100914839  HTR1E; 5-hydroxytryptamine receptor 1E [KO:K04153]
100927922  5-hydroxytryptamine receptor 5B [KO:K04161]
116419427  HTR5A; 5-hydroxytryptamine receptor 5A [KO:K04161]
100914706  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
100928725  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha [KO:K04630]
100916740  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 isoform X1 [KO:K04630]
100914773  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
100930507  GNB1; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 [KO:K04536]
100917513  GNB2; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 [KO:K04537]
100914745  GNB3; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 [KO:K07825]
100932612  GNB4; guanine nucleotide-binding protein subunit beta-4 [KO:K04538]
100931703  GNB5; guanine nucleotide-binding protein subunit beta-5 isoform X1 [KO:K04539]
116419987  GNG3; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3 [KO:K04540]
100917856  GNG4; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-4 [KO:K04541]
100933735  GNG5; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5 [KO:K04542]
100920700  GNG7; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7 [KO:K04543]
100934873  GNG8; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8 [KO:K04544]
116419978  GNG10; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10 [KO:K04545]
100920799  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11 isoform X2 [KO:K04546]
100920266  GNG14; putative guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-14 [KO:K04347]
100914479  GNG12; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12 [KO:K04347]
100927581  GNG13; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-13 [KO:K04547]
100920537  GNGT1; guanine nucleotide-binding protein G(T) subunit gamma-T1 [KO:K04548]
100915783  GNGT2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-T2 [KO:K04549]
100922757  caspase-3-like [KO:K02187] [EC:3.4.22.56]
100922500  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
100923908  DUSP1; dual specificity protein phosphatase 1 [KO:K21278] [EC:3.1.3.16 3.1.3.48]
100929168  ras-like protein [KO:K02833]
116419913  HRAS; GTPase HRas [KO:K02833]
100915526  KRAS; GTPase KRas isoform X1 [KO:K07827]
100927252  ras-related protein Rab-26-like [KO:K07827]
100929426  ras protein let-60-like [KO:K07827]
100928986  NRAS; GTPase NRas [KO:K07828]
100913901  ARAF; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
100934801  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
100935202  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X2 [KO:K04366] [EC:2.7.11.1]
100921899  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
100925240  CACNA1A; voltage-dependent P/Q-type calcium channel subunit alpha-1A isoform X1 [KO:K04344]
100933192  CACNA1B; voltage-dependent N-type calcium channel subunit alpha-1B isoform X1 [KO:K04849]
100926990  KCNJ3; G protein-activated inward rectifier potassium channel 1 [KO:K04997]
100926988  KCNJ6; G protein-activated inward rectifier potassium channel 2 [KO:K05000]
100914987  KCNJ9; G protein-activated inward rectifier potassium channel 3 [KO:K05002]
100928024  KCNJ5; G protein-activated inward rectifier potassium channel 4 [KO:K04999]
100933827  TRPC1; short transient receptor potential channel 1 isoform X1 [KO:K04964]
100927144  sodium-dependent serotonin transporter-like [KO:K05037]
100923444  SLC6A4; sodium-dependent serotonin transporter [KO:K05037]
100919856  amine oxidase [flavin-containing] B isoform X1 [KO:K00274] [EC:1.4.3.4]
100920121  MAOA; amine oxidase [flavin-containing] A isoform X1 [KO:K00274] [EC:1.4.3.4]
Compound
C00076  Calcium cation
C00078  L-Tryptophan
C00165  Diacylglycerol
C00219  Arachidonate
C00238  Potassium cation
C00427  Prostaglandin H2
C00575  3',5'-Cyclic AMP
C00584  Prostaglandin E2
C00639  Prostaglandin F2alpha
C00643  5-Hydroxy-L-tryptophan
C00696  Prostaglandin D2
C00780  Serotonin
C00909  Leukotriene A4
C01245  D-myo-Inositol 1,4,5-trisphosphate
C01330  Sodium cation
C02165  Leukotriene B4
C02166  Leukotriene C4
C02198  Thromboxane A2
C04822  8(R)-HPETE
C05356  5(S)-HPETE
C05635  5-Hydroxyindoleacetate
C05953  Prostaglandin A2
C05954  Prostaglandin B2
C05955  Prostaglandin C2
C05956  Prostaglandin G2
C05957  Prostaglandin J2
C05963  Thromboxane B2
C05964  11-Dehydro-thromboxane B2
C05965  12(S)-HPETE
C05966  15(S)-HPETE
C14768  5,6-EET
C14769  8,9-EET
C14770  11,12-EET
C14771  14,15-EET
C14772  5,6-DHET
C14773  8,9-DHET
C14774  11,12-DHET
C14775  14,15-DHET
C14812  12(R)-HPETE
C14820  11(R)-HPETE
C14821  9(S)-HPETE
C14823  8(S)-HPETE
Reference
PMID:18676031
  Authors
Millan MJ, Marin P, Bockaert J, Mannoury la Cour C
  Title
Signaling at G-protein-coupled serotonin receptors: recent advances and future research directions.
  Journal
Trends Pharmacol Sci 29:454-64 (2008)
DOI:10.1016/j.tips.2008.06.007
Reference
PMID:16896947
  Authors
Bockaert J, Claeysen S, Becamel C, Dumuis A, Marin P
  Title
Neuronal 5-HT metabotropic receptors: fine-tuning of their structure, signaling, and roles in synaptic modulation.
  Journal
Cell Tissue Res 326:553-72 (2006)
DOI:10.1007/s00441-006-0286-1
Reference
PMID:11916537
  Authors
Raymond JR, Mukhin YV, Gelasco A, Turner J, Collinsworth G, Gettys TW, Grewal JS, Garnovskaya MN
  Title
Multiplicity of mechanisms of serotonin receptor signal transduction.
  Journal
Pharmacol Ther 92:179-212 (2001)
DOI:10.1016/S0163-7258(01)00169-3
Reference
PMID:15034221
  Authors
Noda M, Higashida H, Aoki S, Wada K
  Title
Multiple signal transduction pathways mediated by 5-HT receptors.
  Journal
Mol Neurobiol 29:31-9 (2004)
DOI:10.1385/MN:29:1:31
Reference
PMID:20561690
  Authors
Daubert EA, Condron BG
  Title
Serotonin: a regulator of neuronal morphology and circuitry.
  Journal
Trends Neurosci 33:424-34 (2010)
DOI:10.1016/j.tins.2010.05.005
Reference
PMID:16826372
  Authors
Chameau P, van Hooft JA
  Title
Serotonin 5-HT(3) receptors in the central nervous system.
  Journal
Cell Tissue Res 326:573-81 (2006)
DOI:10.1007/s00441-006-0255-8
Reference
PMID:9651340
  Authors
Tournois C, Mutel V, Manivet P, Launay JM, Kellermann O
  Title
Cross-talk between 5-hydroxytryptamine receptors in a serotonergic cell line. Involvement of arachidonic acid metabolism.
  Journal
J Biol Chem 273:17498-503 (1998)
DOI:10.1074/jbc.273.28.17498
Reference
PMID:19545642
  Authors
Iliff JJ, Jia J, Nelson J, Goyagi T, Klaus J, Alkayed NJ
  Title
Epoxyeicosanoid signaling in CNS function and disease.
  Journal
Prostaglandins Other Lipid Mediat 91:68-84 (2010)
DOI:10.1016/j.prostaglandins.2009.06.004
Reference
PMID:12676358
  Authors
Adayev T, Ray I, Sondhi R, Sobocki T, Banerjee P
  Title
The G protein-coupled 5-HT1A receptor causes suppression of caspase-3 through MAPK and protein kinase Calpha.
  Journal
Biochim Biophys Acta 1640:85-96 (2003)
DOI:10.1016/S0167-4889(03)00023-5
Reference
PMID:11701344
  Authors
Albert PR, Tiberi M
  Title
Receptor signaling and structure: insights from serotonin-1 receptors.
  Journal
Trends Endocrinol Metab 12:453-60 (2001)
DOI:10.1016/S1043-2760(01)00498-2
Reference
PMID:9658404
  Authors
Durham PL, Russo AF
  Title
Serotonergic repression of mitogen-activated protein kinase control of the calcitonin gene-related peptide enhancer.
  Journal
Mol Endocrinol 12:1002-9 (1998)
DOI:10.1210/mend.12.7.0135
Reference
PMID:15710402
  Authors
Robert S, Maillet M, Morel E, Launay JM, Fischmeister R, Mercken L, Lezoualc'h F
  Title
Regulation of the amyloid precursor protein ectodomain shedding by the 5-HT4 receptor and Epac.
  Journal
FEBS Lett 579:1136-42 (2005)
DOI:10.1016/j.febslet.2005.01.010
Reference
PMID:12543273
  Authors
Lezoualc'h F, Robert SJ
  Title
The serotonin 5-HT4 receptor and the amyloid precursor protein processing.
  Journal
Exp Gerontol 38:159-66 (2003)
DOI:10.1016/S0531-5565(02)00157-2
Reference
PMID:11043573
  Authors
Durham PL, Russo AF
  Title
Differential regulation of mitogen-activated protein kinase-responsive genes by the duration of a calcium signal.
  Journal
Mol Endocrinol 14:1570-82 (2000)
DOI:10.1210/mend.14.10.0529
Reference
PMID:9542727
  Authors
Hagberg GB, Blomstrand F, Nilsson M, Tamir H, Hansson E
  Title
Stimulation of 5-HT2A receptors on astrocytes in primary culture opens voltage-independent Ca2+ channels.
  Journal
Neurochem Int 32:153-62 (1998)
DOI:10.1016/S0197-0186(97)00087-9
Reference
  Authors
Nestler EJ, Hyman SE, Malenka RC.
  Title
Molecular neuropharmacology: A foundation for clinical neuroscience
  Journal
The McGraw-Hill Companies, Inc. (2001)
Related
pathway
shr00380  Tryptophan metabolism
shr00590  Arachidonic acid metabolism
shr04020  Calcium signaling pathway
shr04721  Synaptic vesicle cycle
shr04976  Bile secretion
KO pathway
ko04726   
LinkDB

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