KEGG   PATHWAY: ko04726Help
ko04726                     Pathway                                

Serotonergic synapse
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.
Organismal Systems; Nervous system
BRITE hierarchy
Pathway map
ko04726  Serotonergic synapse

Ortholog table
H00833  Neurodegeneration with brain iron accumulation (NBIA)
H01161  Aromatic L-amino acid decarboxylase (AADC) deficiency
H01185  Cerebral amyloid angiopathy (CAA)
H01447  Body dysmorphic disorder
H01450  Obsessive-compulsive disorder (OCD)
H01646  Major depressive disorder (MDD)
H01895  Attention deficit hyperactivity disorder (ADHD)
Other DBs
BSID: 525330
GO: 0007210
K00502  tryptophan 5-monooxygenase [EC:]
K01593  aromatic-L-amino-acid/L-tryptophan decarboxylase [EC:]
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:]
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 alpha type [EC:]
K19662  classical protein kinase C beta type [EC:]
K19663  classical protein kinase C gamma type [EC:]
K04371  mitogen-activated protein kinase 1/3 [EC:]
K16342  cytosolic phospholipase A2 [EC:]
K17718  cytochrome P450 family 2 subfamily C polypeptide 8 [EC:]
K17719  cytochrome P450 family 2 subfamily C polypeptide 9 [EC:1.14.14.-]
K17720  cytochrome P450 family 2 subfamily C polypeptide 18 [EC:]
K17721  cytochrome P450 family 2 subfamily C polypeptide 19 [EC:1.14.14.-]
K07413  cytochrome P450 family 2 subfamily C [EC:]
K17712  cytochrome P450 family 2 subfamily D polypeptide 6 [EC:]
K07414  cytochrome P450 family 2 subfamily D [EC:]
K07418  cytochrome P450 family 2 subfamily J [EC:]
K07428  cytochrome P450 family 4 subfamily X [EC:]
K00461  arachidonate 5-lipoxygenase [EC:]
K00458  arachidonate 12-lipoxygenase [EC:]
K08021  arachidonate 12-lipoxygenase (R-type) [EC:1.13.11.-]
K00460  arachidonate 15-lipoxygenase [EC:]
K08022  arachidonate 15-lipoxygenase (second type) / 8-lipoxygenase (S-type) [EC:1.13.11.-]
K00509  prostaglandin-endoperoxide synthase 1 [EC:]
K11987  prostaglandin-endoperoxide synthase 2 [EC:]
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:]
K04345  protein kinase A [EC:]
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 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:]
K21278  dual specificity protein phosphatase 1 [EC:]
K02833  GTPase HRas
K07827  GTPase KRas
K07828  GTPase NRas
K08845  A-Raf proto-oncogene serine/threonine-protein kinase [EC:]
K04365  B-Raf proto-oncogene serine/threonine-protein kinase [EC:]
K04366  RAF proto-oncogene serine/threonine-protein kinase [EC:]
K04368  mitogen-activated protein kinase kinase 1 [EC:]
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:]
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
Millan MJ, Marin P, Bockaert J, Mannoury la Cour C
Signaling at G-protein-coupled serotonin receptors: recent advances and future research directions.
Trends Pharmacol Sci 29:454-64 (2008)
Bockaert J, Claeysen S, Becamel C, Dumuis A, Marin P
Neuronal 5-HT metabotropic receptors: fine-tuning of their structure, signaling, and roles in synaptic modulation.
Cell Tissue Res 326:553-72 (2006)
Raymond JR, Mukhin YV, Gelasco A, Turner J, Collinsworth G, Gettys TW, Grewal JS, Garnovskaya MN
Multiplicity of mechanisms of serotonin receptor signal transduction.
Pharmacol Ther 92:179-212 (2001)
Noda M, Higashida H, Aoki S, Wada K
Multiple signal transduction pathways mediated by 5-HT receptors.
Mol Neurobiol 29:31-9 (2004)
Daubert EA, Condron BG
Serotonin: a regulator of neuronal morphology and circuitry.
Trends Neurosci 33:424-34 (2010)
Chameau P, van Hooft JA
Serotonin 5-HT(3) receptors in the central nervous system.
Cell Tissue Res 326:573-81 (2006)
Tournois C, Mutel V, Manivet P, Launay JM, Kellermann O
Cross-talk between 5-hydroxytryptamine receptors in a serotonergic cell line. Involvement of arachidonic acid metabolism.
J Biol Chem 273:17498-503 (1998)
Iliff JJ, Jia J, Nelson J, Goyagi T, Klaus J, Alkayed NJ
Epoxyeicosanoid signaling in CNS function and disease.
Prostaglandins Other Lipid Mediat 91:68-84 (2010)
Adayev T, Ray I, Sondhi R, Sobocki T, Banerjee P
The G protein-coupled 5-HT1A receptor causes suppression of caspase-3 through MAPK and protein kinase Calpha.
Biochim Biophys Acta 1640:85-96 (2003)
Albert PR, Tiberi M
Receptor signaling and structure: insights from serotonin-1 receptors.
Trends Endocrinol Metab 12:453-60 (2001)
Durham PL, Russo AF
Serotonergic repression of mitogen-activated protein kinase control of the calcitonin gene-related peptide enhancer.
Mol Endocrinol 12:1002-9 (1998)
Robert S, Maillet M, Morel E, Launay JM, Fischmeister R, Mercken L, Lezoualc'h F
Regulation of the amyloid precursor protein ectodomain shedding by the 5-HT4 receptor and Epac.
FEBS Lett 579:1136-42 (2005)
Lezoualc'h F, Robert SJ
The serotonin 5-HT4 receptor and the amyloid precursor protein processing.
Exp Gerontol 38:159-66 (2003)
Durham PL, Russo AF
Differential regulation of mitogen-activated protein kinase-responsive genes by the duration of a calcium signal.
Mol Endocrinol 14:1570-82 (2000)
Hagberg GB, Blomstrand F, Nilsson M, Tamir H, Hansson E
Stimulation of 5-HT2A receptors on astrocytes in primary culture opens voltage-independent Ca2+ channels.
Neurochem Int 32:153-62 (1998)
Nestler EJ, Hyman SE, Malenka RC.
Molecular neuropharmacology: A foundation for clinical neuroscience
The McGraw-Hill Companies, Inc. (2001)

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