KEGG   PATHWAY: ko04726Help
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
BRITE hierarchy
Pathway map
Serotonergic synapse
ko04726

All organismsOrtholog table
Disease
H00833  
Neurodegeneration with brain iron accumulation (NBIA)
H01161  
Aromatic L-amino acid decarboxylase (AADC) deficiency
H01185  
Cerebral amyloid angiopathy (CAA)
Other DBs
BSID: 
GO: 
Orthology
K00502  
tryptophan 5-monooxygenase [EC:1.14.16.4]
K01593  
aromatic-L-amino-acid decarboxylase [EC:4.1.1.28]
K08155  
MFS transporter, DHA1 family, solute carrier family 18 (vesicular amine transporter), member 1/2
K04850  
voltage-dependent calcium channel L type alpha-1C
K04851  
voltage-dependent calcium channel L type alpha-1D
K04853  
voltage-dependent calcium channel L type alpha-1F
K04857  
voltage-dependent calcium channel L type alpha-1S
K04157  
5-hydroxytryptamine receptor 2
K04634  
guanine nucleotide-binding protein G(q) subunit alpha
K05858  
phosphatidylinositol phospholipase C, beta [EC:3.1.4.11]
K04958  
inositol 1,4,5-triphosphate receptor type 1
K04959  
inositol 1,4,5-triphosphate receptor type 2
K04960  
inositol 1,4,5-triphosphate receptor type 3
K02677  
classical protein kinase C [EC:2.7.11.13]
K04371  
extracellular signal-regulated kinase 1/2 [EC:2.7.11.24]
K16342  
cytosolic phospholipase A2 [EC:3.1.1.4]
K07413  
cytochrome P450, family 2, subfamily C [EC:1.14.14.1]
K07414  
cytochrome P450, family 2, subfamily D [EC:1.14.14.1]
K07418  
cytochrome P450, family 2, subfamily J [EC:1.14.14.1]
K07428  
cytochrome P450, family 4, subfamily X [EC:1.14.14.1]
K00461  
arachidonate 5-lipoxygenase [EC:1.13.11.34]
K00458  
arachidonate 12-lipoxygenase [EC:1.13.11.31]
K08021  
arachidonate 12-lipoxygenase (R-type) [EC:1.13.11.-]
K00460  
arachidonate 15-lipoxygenase [EC:1.13.11.33]
K08022  
arachidonate 15-lipoxygenase (second type) / 8-lipoxygenase (S-type) [EC:1.13.11.- 1.13.11.33]
K00509  
prostaglandin-endoperoxide synthase 1 [EC:1.14.99.1]
K11987  
prostaglandin-endoperoxide synthase 2 [EC:1.14.99.1]
K04819  
5-hydroxytryptamine receptor 3
K04160  
5-hydroxytryptamine receptor 4
K04162  
5-hydroxytryptamine receptor 6
K04163  
5-hydroxytryptamine receptor 7
K04632  
guanine nucleotide-binding protein G(s) subunit alpha
K08045  
adenylate cyclase 5 [EC:4.6.1.1]
K04345  
protein kinase A [EC:2.7.11.11]
K04943  
potassium intermediate/small conductance calcium-activated channel subfamily N member 2
K04892  
potassium voltage-gated channel Shal-related subfamily D member 2
K05181  
gamma-aminobutyric acid receptor subunit beta
K08014  
Rap guanine nucleotide exchange factor (GEF) 3
K04520  
amyloid beta A4 protein
K04153  
5-hydroxytryptamine receptor 1
K04161  
5-hydroxytryptamine receptor 5
K04630  
guanine nucleotide-binding protein G(i) subunit alpha
K04534  
guanine nucleotide-binding protein G(o) subunit alpha
K04536  
guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
K04537  
guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2
K07825  
guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3
K04538  
guanine nucleotide-binding protein subunit beta-4
K04539  
guanine nucleotide-binding protein subunit beta-5
K07826  
guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
K04540  
guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3
K04541  
guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-4
K04542  
guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5
K04543  
guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7
K04544  
guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8
K04545  
guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10
K04546  
guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11
K04347  
guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12
K04547  
guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-13
K04548  
guanine nucleotide-binding protein G(T) subunit gamma-T1
K04549  
guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-T2
K02187  
caspase 3 [EC:3.4.22.56]
K02833  
GTPase HRas
K07827  
GTPase KRas
K07828  
GTPase NRas
K08845  
A-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]
K04365  
B-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]
K04366  
RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]
K04368  
mitogen-activated protein kinase kinase 1 [EC:2.7.12.2]
K04344  
voltage-dependent calcium channel P/Q type alpha-1A
K04849  
voltage-dependent calcium channel N type alpha-1B
K04997  
potassium inwardly-rectifying channel subfamily J member 3
K05000  
potassium inwardly-rectifying channel subfamily J member 6
K05002  
potassium inwardly-rectifying channel subfamily J member 9
K04999  
potassium inwardly-rectifying channel subfamily J member 5
K04964  
transient receptor potential cation channel subfamily C member 1
K05037  
solute carrier family 6 (neurotransmitter transporter, serotonin) member 4
K00274  
monoamine oxidase [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
  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)
Reference
  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)
Reference
  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)
Reference
  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)
Reference
  Authors
Daubert EA, Condron BG
  Title
Serotonin: a regulator of neuronal morphology and circuitry.
  Journal
Trends Neurosci 33:424-34 (2010)
Reference
  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)
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)
Reference
  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)
Reference
  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)
Reference
  Authors
Albert PR, Tiberi M
  Title
Receptor signaling and structure: insights from serotonin-1 receptors.
  Journal
Trends Endocrinol Metab 12:453-60 (2001)
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)
Reference
  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)
Reference
  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)
Reference
  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)
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)
Reference
  Authors
Nestler EJ, Hyman SE, Malenka RC.
  Title
Molecular neuropharmacology: A foundation for clinical neuroscience
  Journal
The McGraw-Hill Companies, Inc. (2001)
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