KEGG   PATHWAY: rno04726
Entry
rno04726                    Pathway                                
Name
Serotonergic synapse - Rattus norvegicus (rat)
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
rno04726  Serotonergic synapse
rno04726

Other DBs
GO: 0007210
Organism
Rattus norvegicus (rat) [GN:rno]
Gene
317675  Tph2; tryptophan 5-hydroxylase 2 [KO:K00502] [EC:1.14.16.4]
24848  Tph1; tryptophan 5-hydroxylase 1 [KO:K00502] [EC:1.14.16.4]
24311  Ddc; aromatic-L-amino-acid decarboxylase isoform a [KO:K01593] [EC:4.1.1.28 4.1.1.105]
25549  Slc18a2; synaptic vesicular amine transporter [KO:K08155]
25693  Slc18a1; chromaffin granule amine transporter [KO:K08155]
24239  Cacna1c; voltage-dependent L-type calcium channel subunit alpha-1C [KO:K04850]
29716  Cacna1d; voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851]
114493  Cacna1f; voltage-dependent L-type calcium channel subunit alpha-1F [KO:K04853]
682930  Cacna1s; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
29595  Htr2a; 5-hydroxytryptamine receptor 2A [KO:K04157]
29581  Htr2b; 5-hydroxytryptamine receptor 2B [KO:K04157]
25187  Htr2c; 5-hydroxytryptamine receptor 2C precursor [KO:K04157]
81666  Gnaq; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
24654  Plcb1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
29322  Plcb3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
85240  Plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
25031  Plcb4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
25262  Itpr1; inositol 1,4,5-trisphosphate receptor type 1 isoform 3 [KO:K04958]
81678  Itpr2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
25679  Itpr3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
24680  Prkca; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
25023  Prkcb; protein kinase C beta type isoform 2 [KO:K19662] [EC:2.7.11.13]
24681  Prkcg; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
116590  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
50689  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
296091  Pla2g4e; cytosolic phospholipase A2 epsilon isoform X1 [KO:K16342] [EC:3.1.1.4]
24653  Pla2g4a; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
311341  Pla2g4b; cytosolic phospholipase A2 beta [KO:K16342] [EC:3.1.1.4]
691905  Pla2g4d; cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
691907  Pla2g4f; cytosolic phospholipase A2 zeta isoform X1 [KO:K16342] [EC:3.1.1.4]
691810  Pla2g4c; cytosolic phospholipase A2 gamma [KO:K16342] [EC:3.1.1.4]
83790  Cyp2c23; cytochrome P450 2C23 [KO:K07413] [EC:1.14.14.1]
29298  Cyp2c7; cytochrome P450 2C7 precursor [KO:K07413] [EC:1.14.14.1]
171518  Cyp2c22; cytochrome P450 2C70 precursor [KO:K07413] [EC:1.14.14.1]
25011  Cyp2c12; cytochrome P450 2C12, female-specific precursor [KO:K07413] [EC:1.14.14.1]
171521  Cyp2c13; cytochrome P450 2C13, male-specific [KO:K07413] [EC:1.14.14.1]
29277  Cyp2c11; cytochrome P450 2C11 [KO:K07413] [EC:1.14.14.1]
499353  Cyp2c24; cytochrome P450, family 2, subfamily c, polypeptide 24 precursor [KO:K07413] [EC:1.14.14.1]
100912265  Cyp2c66; cytochrome P450 2C42-like isoform X1 [KO:K07413] [EC:1.14.14.1]
100361492  Cyp2c55; cytochrome P450 2C55 precursor [KO:K07413] [EC:1.14.14.1]
100361547  Cyp2c7l1; cytochrome P450 2C7-like [KO:K07413] [EC:1.14.14.1]
120098584  cytochrome P450 2C7-like isoform X1 [KO:K07413] [EC:1.14.14.1]
120093077  cytochrome P450 2C6 isoform X1 [KO:K07413] [EC:1.14.14.1]
293989  Cyp2c6v1; cytochrome P450 2C6 precursor [KO:K07413] [EC:1.14.14.1]
100911718  cytochrome P450 2C6 isoform X1 [KO:K07413] [EC:1.14.14.1]
171522  Cyp2d4; cytochrome P450 2D4 [KO:K07414] [EC:1.14.14.1]
266684  Cyp2d1; cytochrome P450 2D1 [KO:K07414] [EC:1.14.14.1]
24303  Cyp2d3; cytochrome P450 2D3 [KO:K07414] [EC:1.14.14.1]
25053  Cyp2d2; cytochrome P450 2D26 [KO:K07414] [EC:1.14.14.1]
286963  Cyp2d5; cytochrome P450 2D10 [KO:K07414] [EC:1.14.14.1]
502969  Cyp2j16; cytochrome P450 2J4-like isoform X1 [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
313375  Cyp2j3; cytochrome P450 2J3 [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
313373  Cyp2j10; cytochrome P450, family 2, subfamily j, polypeptide 10 [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
100912642  cytochrome P450 2J4-like [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
65210  Cyp2j4; cytochrome P450 2J4 [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
246767  Cyp4x1; cytochrome P450 4X1 [KO:K07428] [EC:1.14.14.1]
25290  Alox5; polyunsaturated fatty acid 5-lipoxygenase [KO:K00461] [EC:1.13.11.34]
287454  Alox12; polyunsaturated fatty acid lipoxygenase ALOX12 [KO:K00458] [EC:1.13.11.31]
303252  Alox12e; polyunsaturated fatty acid (12S)/(13S)-lipoxygenase, epidermal-type [KO:K00458] [EC:1.13.11.31]
287425  Alox12b; arachidonate 12-lipoxygenase, 12R-type [KO:K08021] [EC:1.13.11.-]
81639  Alox15; polyunsaturated fatty acid lipoxygenase ALOX15 [KO:K00460] [EC:1.13.11.33]
266604  Alox15b; polyunsaturated fatty acid lipoxygenase ALOX15B [KO:K08022] [EC:1.13.11.33 1.13.11.-]
24693  Ptgs1; prostaglandin G/H synthase 1 precursor [KO:K00509] [EC:1.14.99.1]
29527  Ptgs2; prostaglandin G/H synthase 2 precursor [KO:K11987] [EC:1.14.99.1]
79246  Htr3a; 5-hydroxytryptamine receptor 3A precursor [KO:K04819]
58963  Htr3b; 5-hydroxytryptamine receptor 3B precursor [KO:K04819]
25324  Htr4; 5-hydroxytryptamine receptor 4 [KO:K04160]
64354  Htr6; 5-hydroxytryptamine receptor 6 [KO:K04162]
65032  Htr7; 5-hydroxytryptamine receptor 7 [KO:K04163]
24896  Gnas; SCG6 (secretogranin VI) isoform SCG6 precursor [KO:K04632]
64532  Adcy5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
25636  Prkaca; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
293508  Prkacb; cAMP-dependent protein kinase catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
54262  Kcnn2; small conductance calcium-activated potassium channel protein 2 isoform 2 [KO:K04943]
65180  Kcnd2; potassium voltage-gated channel subfamily D member 2 [KO:K04892]
25450  Gabrb1; gamma-aminobutyric acid receptor subunit beta-1 precursor [KO:K05181]
24922  Gabrb3; gamma-aminobutyric acid receptor subunit beta-3 precursor [KO:K05181]
25451  Gabrb2; gamma-aminobutyric acid receptor subunit beta-2 precursor [KO:K05181]
59326  Rapgef3; rap guanine nucleotide exchange factor 3 [KO:K08014]
54226  App; amyloid-beta precursor protein precursor [KO:K04520]
24473  Htr1a; 5-hydroxytryptamine receptor 1A [KO:K04153]
25075  Htr1b; 5-hydroxytryptamine receptor 1B [KO:K04153]
25323  Htr1d; 5-hydroxytryptamine receptor 1D [KO:K04153]
60448  Htr1f; 5-hydroxytryptamine receptor 1F [KO:K04153]
25689  Htr5a; 5-hydroxytryptamine receptor 5A [KO:K04161]
79247  Htr5b; 5-hydroxytryptamine receptor 5B [KO:K04161]
25686  Gnai1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
25643  Gnai3; guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630]
81664  Gnai2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
50664  Gnao1; guanine nucleotide-binding protein G(o) subunit alpha isoform B [KO:K04534]
24400  Gnb1; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 [KO:K04536]
81667  Gnb2; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 [KO:K04537]
60449  Gnb3; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 [KO:K07825]
294962  Gnb4; guanine nucleotide-binding protein subunit beta-4 [KO:K04538]
83579  Gnb5; guanine nucleotide-binding protein subunit beta-5 [KO:K04539]
80850  Gng2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 [KO:K07826]
114117  Gng3; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3 [KO:K04540]
114118  Gng4; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-4 [KO:K04541]
79218  Gng5; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5 [KO:K04542]
58979  Gng7; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7 [KO:K04543]
245986  Gng8; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8 [KO:K04544]
114119  Gng10; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10 [KO:K04545]
64199  Gng11; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11 [KO:K04546]
114120  Gng12; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12 [KO:K04347]
685513  Gng14; putative guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-14 [KO:K04347]
685451  Gng13; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-13 [KO:K04547]
680149  Gngt1; guanine nucleotide-binding protein G(T) subunit gamma-T1 [KO:K04548]
690825  Gngt2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-T2 [KO:K04549]
25402  Casp3; caspase-3 [KO:K02187] [EC:3.4.22.56]
114856  Dusp1; dual specificity protein phosphatase 1 [KO:K21278] [EC:3.1.3.16 3.1.3.48]
293621  Hras; GTPase HRas [KO:K02833]
367858  Hrasl1; HRas proto-oncogene, GTPase like 1 [KO:K02833]
24525  Kras; GTPase KRas [KO:K07827]
24605  Nras; GTPase NRas [KO:K07828]
64363  Araf; serine/threonine-protein kinase A-Raf isoform 1 [KO:K08845] [EC:2.7.11.1]
114486  Braf; serine/threonine-protein kinase B-raf isoform X2 [KO:K04365] [EC:2.7.11.1]
24703  Raf1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
170851  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
25398  Cacna1a; voltage-dependent P/Q-type calcium channel subunit alpha-1A [KO:K04344]
257648  Cacna1b; voltage-dependent N-type calcium channel subunit alpha-1B isoform 1 [KO:K04849]
50599  Kcnj3; G protein-activated inward rectifier potassium channel 1 [KO:K04997]
25743  Kcnj6; G protein-activated inward rectifier potassium channel 2 isoform 1 [KO:K05000]
116560  Kcnj9; G protein-activated inward rectifier potassium channel 3 [KO:K05002]
29713  Kcnj5; G protein-activated inward rectifier potassium channel 4 [KO:K04999]
89821  Trpc1; short transient receptor potential channel 1 isoform 2 [KO:K04964]
25553  Slc6a4; sodium-dependent serotonin transporter [KO:K05037]
25750  Maob; amine oxidase [flavin-containing] B [KO:K00274] [EC:1.4.3.4]
29253  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
rno00380  Tryptophan metabolism
rno00590  Arachidonic acid metabolism
rno04020  Calcium signaling pathway
rno04721  Synaptic vesicle cycle
rno04976  Bile secretion
KO pathway
ko04726   
LinkDB

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