KEGG   PATHWAY: opi04726
Entry
opi04726                    Pathway                                
Name
Serotonergic synapse - Ochotona princeps (American pika)
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
opi04726  Serotonergic synapse
opi04726

Other DBs
GO: 0007210
Organism
Ochotona princeps (American pika) [GN:opi]
Gene
101524788  TPH2; tryptophan 5-hydroxylase 2 isoform X2 [KO:K00502] [EC:1.14.16.4]
101517264  TPH1; tryptophan 5-hydroxylase 1 [KO:K00502] [EC:1.14.16.4]
101533722  DDC; aromatic-L-amino-acid decarboxylase [KO:K01593] [EC:4.1.1.28 4.1.1.105]
101522326  SLC18A1; chromaffin granule amine transporter [KO:K08155]
101535906  SLC18A2; synaptic vesicular amine transporter [KO:K08155]
101536063  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
101524545  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
101519864  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853]
101529015  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
101533834  HTR2C; 5-hydroxytryptamine receptor 2C isoform X1 [KO:K04157]
101520543  HTR2B; 5-hydroxytryptamine receptor 2B [KO:K04157]
101516626  HTR2A; 5-hydroxytryptamine receptor 2A isoform X1 [KO:K04157]
101517012  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
101524349  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
101524739  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
101529337  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
101520538  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X2 [KO:K05858] [EC:3.1.4.11]
101524859  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
101526097  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
101516441  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X2 [KO:K04960]
101523549  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
101523439  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
101534827  PRKCG; protein kinase C gamma type isoform X1 [KO:K19663] [EC:2.7.11.13]
101530701  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
101525427  mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
101523982  PLA2G4F; cytosolic phospholipase A2 zeta [KO:K16342] [EC:3.1.1.4]
101524217  PLA2G4D; cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
101524453  PLA2G4E; cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]
101524927  PLA2G4B; cytosolic phospholipase A2 beta [KO:K16342] [EC:3.1.1.4]
101520966  PLA2G4A; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
101517442  PLA2G4C; cytosolic phospholipase A2 gamma [KO:K16342] [EC:3.1.1.4]
101524463  cytochrome P450 2C18-like isoform X1 [KO:K17720] [EC:1.14.14.1]
101530346  cytochrome P450 2C41-like isoform X2 [KO:K17720] [EC:1.14.14.1]
101519910  cytochrome P450 2C18-like [KO:K07413] [EC:1.14.14.1]
101525811  cytochrome P450 2C5-like isoform X1 [KO:K07413] [EC:1.14.14.1]
101526220  cytochrome P450 2C15-like isoform X2 [KO:K07413] [EC:1.14.14.1]
101526786  cytochrome P450 2C5-like isoform X1 [KO:K07413] [EC:1.14.14.1]
101527195  cytochrome P450 2C2 isoform X1 [KO:K07413] [EC:1.14.14.1]
101527783  cytochrome P450 2C14-like isoform X1 [KO:K07413] [EC:1.14.14.1]
101528381  cytochrome P450 2C14-like isoform X1 [KO:K07413] [EC:1.14.14.1]
101528927  cytochrome P450 2C14-like isoform X1 [KO:K07413] [EC:1.14.14.1]
101529516  cytochrome P450 2C1-like isoform X2 [KO:K07413] [EC:1.14.14.1]
101529922  cytochrome P450 2C1-like isoform X1 [KO:K07413] [EC:1.14.14.1]
101520157  cytochrome P450 2C19-like [KO:K07413] [EC:1.14.14.1]
101520641  LOW QUALITY PROTEIN: cytochrome P450 2C3-like [KO:K07413] [EC:1.14.14.1]
101519662  cytochrome P450 2C31-like [KO:K07413] [EC:1.14.14.1]
101524854  cytochrome P450 2C30-like isoform X2 [KO:K07413] [EC:1.14.14.1]
101534880  cytochrome P450 2D17-like isoform X1 [KO:K17712] [EC:1.14.14.1]
101535547  LOW QUALITY PROTEIN: cytochrome P450 2D17-like [KO:K07414] [EC:1.14.14.1]
101535122  LOW QUALITY PROTEIN: cytochrome P450 2D17-like [KO:K07414] [EC:1.14.14.1]
101535375  cytochrome P450 2D17-like isoform X1 [KO:K07414] [EC:1.14.14.1]
101531516  cytochrome P450 2J1-like [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
101531357  cytochrome P450 2J1 [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
101531303  cytochrome P450 4X1-like [KO:K07428] [EC:1.14.14.1]
101531548  cytochrome P450 4X1 [KO:K07428] [EC:1.14.14.1]
101534185  ALOX5; polyunsaturated fatty acid 5-lipoxygenase [KO:K00461] [EC:1.13.11.34]
101518253  ALOX12; polyunsaturated fatty acid lipoxygenase ALOX12 [KO:K00458] [EC:1.13.11.31]
101524903  ALOX12B; arachidonate 12-lipoxygenase, 12R-type [KO:K08021] [EC:1.13.11.-]
101518498  ALOX15; polyunsaturated fatty acid lipoxygenase ALOX15 [KO:K00460] [EC:1.13.11.33]
101525136  ALOX15B; polyunsaturated fatty acid lipoxygenase ALOX15B isoform X1 [KO:K08022] [EC:1.13.11.33 1.13.11.-]
101534818  PTGS1; prostaglandin G/H synthase 1 [KO:K00509] [EC:1.14.99.1]
101536557  PTGS2; prostaglandin G/H synthase 2 [KO:K11987] [EC:1.14.99.1]
101522122  HTR3B; 5-hydroxytryptamine receptor 3B [KO:K04819]
101532254  5-hydroxytryptamine receptor 3C [KO:K04819]
101517397  HTR3A; 5-hydroxytryptamine receptor 3A [KO:K04819]
101532495  LOW QUALITY PROTEIN: 5-hydroxytryptamine receptor 3C-like [KO:K04819]
101520829  HTR4; 5-hydroxytryptamine receptor 4 [KO:K04160]
101516289  HTR6; 5-hydroxytryptamine receptor 6 [KO:K04162]
101521700  HTR7; 5-hydroxytryptamine receptor 7 isoform X1 [KO:K04163]
101526074  neuroendocrine secretory protein 55-like [KO:K04632]
101526286  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
101534210  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
101525119  cAMP-dependent protein kinase catalytic subunit alpha-like [KO:K04345] [EC:2.7.11.11]
101516221  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
101527560  KCNN2; small conductance calcium-activated potassium channel protein 2 [KO:K04943]
101520929  KCND2; potassium voltage-gated channel subfamily D member 2 [KO:K04892]
101521533  GABRB1; gamma-aminobutyric acid receptor subunit beta-1 [KO:K05181]
101520585  GABRB2; gamma-aminobutyric acid receptor subunit beta-2 isoform X1 [KO:K05181]
101517107  GABRB3; gamma-aminobutyric acid receptor subunit beta-3 isoform X1 [KO:K05181]
101523807  RAPGEF3; rap guanine nucleotide exchange factor 3 [KO:K08014]
101518476  amyloid-beta precursor protein isoform X1 [KO:K04520]
101529679  HTR1A; 5-hydroxytryptamine receptor 1A [KO:K04153]
101531032  HTR1D; 5-hydroxytryptamine receptor 1D [KO:K04153]
101519249  HTR1E; 5-hydroxytryptamine receptor 1E [KO:K04153]
101528037  HTR1B; 5-hydroxytryptamine receptor 1B [KO:K04153]
101525547  HTR1F; 5-hydroxytryptamine receptor 1F [KO:K04153]
101527482  5-hydroxytryptamine receptor 5B-like [KO:K04161]
101533055  HTR5A; 5-hydroxytryptamine receptor 5A [KO:K04161]
101525340  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha [KO:K04630]
101516368  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
101531957  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
101524943  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
101525483  GNB1; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 [KO:K04536]
101529615  GNB2; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 [KO:K04537]
101536793  GNB3; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 isoform X1 [KO:K07825]
101530547  GNB4; guanine nucleotide-binding protein subunit beta-4 [KO:K04538]
101532346  GNB5; guanine nucleotide-binding protein subunit beta-5 [KO:K04539]
101528942  GNG2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 [KO:K07826]
101528746  GNG3; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3 [KO:K04540]
101531710  GNG4; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-4 [KO:K04541]
101521396  GNG5; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5 [KO:K04542]
101516538  GNG7; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7 [KO:K04543]
101516227  GNG8; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8 [KO:K04544]
101531323  GNG10; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10 [KO:K04545]
101531879  GNG11; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11 [KO:K04546]
101524512  GNG14; putative guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-14 [KO:K04347]
101519866  GNG12; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12 [KO:K04347]
101535404  GNG13; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-13 [KO:K04547]
101531647  GNGT1; guanine nucleotide-binding protein G(T) subunit gamma-T1 [KO:K04548]
101534148  GNGT2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-T2 [KO:K04549]
101531640  CASP3; caspase-3 isoform X1 [KO:K02187] [EC:3.4.22.56]
101531665  DUSP1; dual specificity protein phosphatase 1 [KO:K21278] [EC:3.1.3.16 3.1.3.48]
101531636  HRAS; GTPase HRas [KO:K02833]
101534080  KRAS; GTPase KRas isoform X1 [KO:K07827]
101524465  NRAS; GTPase NRas [KO:K07828]
101529871  ARAF; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
101526188  BRAF; serine/threonine-protein kinase B-raf isoform X2 [KO:K04365] [EC:2.7.11.1]
101534290  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X2 [KO:K04366] [EC:2.7.11.1]
101533612  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
101520695  CACNA1A; voltage-dependent P/Q-type calcium channel subunit alpha-1A isoform X3 [KO:K04344]
101523955  CACNA1B; voltage-dependent N-type calcium channel subunit alpha-1B [KO:K04849]
101532095  KCNJ3; G protein-activated inward rectifier potassium channel 1 isoform X1 [KO:K04997]
101525377  KCNJ6; G protein-activated inward rectifier potassium channel 2 [KO:K05000]
101528958  KCNJ9; G protein-activated inward rectifier potassium channel 3 [KO:K05002]
101526431  KCNJ5; G protein-activated inward rectifier potassium channel 4 [KO:K04999]
101516309  TRPC1; short transient receptor potential channel 1 isoform X1 [KO:K04964]
101524353  SLC6A4; sodium-dependent serotonin transporter [KO:K05037]
101517738  MAOB; amine oxidase [flavin-containing] B [KO:K00274] [EC:1.4.3.4]
101517490  MAOA; amine oxidase [flavin-containing] A [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
opi00380  Tryptophan metabolism
opi00590  Arachidonic acid metabolism
opi04020  Calcium signaling pathway
opi04721  Synaptic vesicle cycle
opi04976  Bile secretion
KO pathway
ko04726   
LinkDB

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