KEGG   PATHWAY: ko04726
Entry
ko04726                     Pathway                                
Name
Serotonergic synapse
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
ko04726  Serotonergic synapse
ko04726

Other DBs
GO: 0007210
Orthology
K00274  MAO, aofH; monoamine oxidase [EC:1.4.3.4]
K00458  ALOX12; arachidonate 12-lipoxygenase [EC:1.13.11.31]
K00460  ALOX15; arachidonate 15-lipoxygenase [EC:1.13.11.33]
K00461  ALOX5; arachidonate 5-lipoxygenase [EC:1.13.11.34]
K00502  TPH1_2; tryptophan 5-monooxygenase [EC:1.14.16.4]
K00509  PTGS1, COX1; prostaglandin-endoperoxide synthase 1 [EC:1.14.99.1]
K01593  DDC, TDC; aromatic-L-amino-acid/L-tryptophan decarboxylase [EC:4.1.1.28 4.1.1.105]
K02187  CASP3; caspase 3 [EC:3.4.22.56]
K02677  PRKCA; classical protein kinase C alpha type [EC:2.7.11.13]
K02833  HRAS; GTPase HRas
K04153  HTR1; 5-hydroxytryptamine receptor 1
K04157  HTR2; 5-hydroxytryptamine receptor 2
K04160  HTR4; 5-hydroxytryptamine receptor 4
K04161  HTR5; 5-hydroxytryptamine receptor 5
K04162  HTR6; 5-hydroxytryptamine receptor 6
K04163  HTR7; 5-hydroxytryptamine receptor 7
K04344  CACNA1A, CAV2.1; voltage-dependent calcium channel P/Q type alpha-1A
K04345  PKA; protein kinase A [EC:2.7.11.11]
K04347  GNG12; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12
K04365  BRAF; B-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]
K04366  RAF1; RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]
K04368  MAP2K1, MEK1; mitogen-activated protein kinase kinase 1 [EC:2.7.12.2]
K04371  ERK, MAPK1_3; mitogen-activated protein kinase 1/3 [EC:2.7.11.24]
K04520  APP; amyloid beta A4 protein
K04534  GNAO, G-ALPHA-O; guanine nucleotide-binding protein G(o) subunit alpha
K04536  GNB1; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
K04537  GNB2; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2
K04538  GNB4; guanine nucleotide-binding protein subunit beta-4
K04539  GNB5; guanine nucleotide-binding protein subunit beta-5
K04540  GNG3; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3
K04541  GNG4; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-4
K04542  GNG5; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5
K04543  GNG7; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7
K04544  GNG8; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8
K04545  GNG10; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10
K04546  GNG11; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11
K04547  GNG13; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-13
K04548  GNGT1; guanine nucleotide-binding protein G(T) subunit gamma-T1
K04549  GNGT2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-T2
K04630  GNAI; guanine nucleotide-binding protein G(i) subunit alpha
K04632  GNAS; guanine nucleotide-binding protein G(s) subunit alpha
K04634  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha
K04819  HTR3; 5-hydroxytryptamine receptor 3
K04849  CACNA1B, CAV2.2; voltage-dependent calcium channel N type alpha-1B
K04850  CACNA1C, CAV1.2; voltage-dependent calcium channel L type alpha-1C
K04851  CACNA1D, CAV1.3; voltage-dependent calcium channel L type alpha-1D
K04853  CACNA1F, CAV1.4; voltage-dependent calcium channel L type alpha-1F
K04857  CACNA1S, CAV1.1; voltage-dependent calcium channel L type alpha-1S
K04892  KCND2, KV4.2; potassium voltage-gated channel Shal-related subfamily D member 2
K04943  KCNN2, KCA2.2; potassium intermediate/small conductance calcium-activated channel subfamily N member 2
K04958  ITPR1; inositol 1,4,5-triphosphate receptor type 1
K04959  ITPR2; inositol 1,4,5-triphosphate receptor type 2
K04960  ITPR3; inositol 1,4,5-triphosphate receptor type 3
K04964  TRPC1; transient receptor potential cation channel subfamily C member 1
K04997  KCNJ3, KIR3.1; potassium inwardly-rectifying channel subfamily J member 3
K04999  KCNJ5, KIR3.4; potassium inwardly-rectifying channel subfamily J member 5
K05000  KCNJ6, KIR3.2; potassium inwardly-rectifying channel subfamily J member 6
K05002  KCNJ9, KIR3.3; potassium inwardly-rectifying channel subfamily J member 9
K05037  SLC6A4, SERT; solute carrier family 6 (neurotransmitter transporter, serotonin) member 4
K05181  GABRB; gamma-aminobutyric acid receptor subunit beta
K05858  PLCB; phosphatidylinositol phospholipase C, beta [EC:3.1.4.11]
K07413  CYP2C; cytochrome P450 family 2 subfamily C [EC:1.14.14.1]
K07414  CYP2D; cytochrome P450 family 2 subfamily D [EC:1.14.14.1]
K07418  CYP2J; cytochrome P450 family 2 subfamily J [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
K07428  CYP4X; cytochrome P450 family 4 subfamily X [EC:1.14.14.1]
K07825  GNB3; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3
K07826  GNG2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
K07827  KRAS, KRAS2; GTPase KRas
K07828  NRAS; GTPase NRas
K08014  RAPGEF3, EPAC1; Rap guanine nucleotide exchange factor 3
K08021  ALOX12B; arachidonate 12-lipoxygenase (R-type) [EC:1.13.11.-]
K08022  ALOX15B; arachidonate 15-lipoxygenase (second type) / 8-lipoxygenase (S-type) [EC:1.13.11.33 1.13.11.-]
K08045  ADCY5; adenylate cyclase 5 [EC:4.6.1.1]
K08155  SLC18A1_2, VMAT; MFS transporter, DHA1 family, solute carrier family 18 (vesicular amine transporter), member 1/2
K08845  ARAF, ARAF1; A-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]
K11987  PTGS2, COX2; prostaglandin-endoperoxide synthase 2 [EC:1.14.99.1]
K16342  PLA2G4, CPLA2; cytosolic phospholipase A2 [EC:3.1.1.4]
K17712  CYP2D6; cytochrome P450 family 2 subfamily D6 [EC:1.14.14.1]
K17718  CYP2C8; cytochrome P450 family 2 subfamily C8 [EC:1.14.14.1]
K17719  CYP2C9; cytochrome P450 family 2 subfamily C9 [EC:1.14.14.51 1.14.14.52 1.14.14.53 1.14.14.-]
K17720  CYP2C18; cytochrome P450 family 2 subfamily C18 [EC:1.14.14.1]
K17721  CYP2C19; cytochrome P450 family 2 subfamily C19 [EC:1.14.14.51 1.14.14.52 1.14.14.53 1.14.14.75 1.14.14.-]
K19662  PRKCB; classical protein kinase C beta type [EC:2.7.11.13]
K19663  PRKCG; classical protein kinase C gamma type [EC:2.7.11.13]
K21278  DUSP1; dual specificity protein phosphatase 1 [EC:3.1.3.16 3.1.3.48]
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
ko00380  Tryptophan metabolism
ko00590  Arachidonic acid metabolism
ko04020  Calcium signaling pathway
ko04721  Synaptic vesicle cycle
ko04976  Bile secretion

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