KEGG   PATHWAY: ko04082
Entry
ko04082                     Pathway                                
Name
Neuroactive ligand signaling
Description
Neuroactive ligand signaling is a process where receptors and ligands on the cell membrane initiate intracellular signaling pathways. It plays a crucial role in the development of various brain disorders.
Class
Environmental Information Processing; Signaling molecules and interaction
Pathway map
ko04082  Neuroactive ligand signaling
ko04082

Orthology
K00623  CHAT; choline O-acetyltransferase [EC:2.3.1.6]
K01049  ACHE; acetylcholinesterase [EC:3.1.1.7]
K02677  PRKCA; classical protein kinase C alpha type [EC:2.7.11.13]
K04129  CHRM1; muscarinic acetylcholine receptor M1
K04130  CHRM2; muscarinic acetylcholine receptor M2
K04131  CHRM3; muscarinic acetylcholine receptor M3
K04132  CHRM4; muscarinic acetylcholine receptor M4
K04133  CHRM5; muscarinic acetylcholine receptor M5
K04135  ADRA1A; adrenergic receptor alpha-1A
K04136  ADRA1B; adrenergic receptor alpha-1B
K04137  ADRA1D; adrenergic receptor alpha-1D
K04138  ADRA2A; adrenergic receptor alpha-2A
K04139  ADRA2B; adrenergic receptor alpha-2B
K04140  ADRA2C; adrenergic receptor alpha-2C
K04141  ADRB1; adrenergic receptor beta-1
K04142  ADRB2; adrenergic receptor beta-2
K04144  DRD1; dopamine receptor D1
K04145  DRD2; dopamine receptor D2
K04146  DRD3; dopamine receptor D3
K04147  DRD4; dopamine receptor D4
K04149  HRH1; histamine receptor H1
K04150  HRH2; histamine receptor H2
K04151  HRH3; histamine receptor H3
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
K04201  MC3R; melanocortin 3 receptor
K04202  MC4R; melanocortin 4 receptor
K04213  OPRD1; delta-type opioid receptor
K04214  OPRK1; kappa-type opioid receptor
K04215  OPRM1; mu-type opioid receptor
K04216  OPRL1; nociceptin receptor
K04222  TACR1; tachykinin receptor 1
K04223  TACR2; tachykinin receptor 2
K04224  TACR3; tachykinin receptor 3
K04265  ADORA1; adenosine receptor A1
K04266  ADORA2A, ADOR; adenosine receptor A2a
K04267  ADORA2B; adenosine receptor A2b
K04268  ADORA3; adenosine receptor A3
K04269  P2RY2; P2Y purinoceptor 2
K04270  P2RY1; P2Y purinoceptor 1
K04271  P2RY4; P2Y purinoceptor 4
K04272  P2RY6; P2Y purinoceptor 6
K04298  P2RY12; P2Y purinoceptor 12
K04299  P2RY14; P2Y purinoceptor 14
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
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
K04603  GRM1; metabotropic glutamate receptor 1
K04604  GRM5; metabotropic glutamate receptor 5
K04605  GRM2; metabotropic glutamate receptor 2
K04606  GRM3; metabotropic glutamate receptor 3
K04607  GRM4; metabotropic glutamate receptor 4
K04608  GRM6; metabotropic glutamate receptor 6
K04609  GRM7; metabotropic glutamate receptor 7
K04610  GRM8; metabotropic glutamate receptor 8
K04615  GABBR; gamma-aminobutyric acid type B receptor
K04630  GNAI; guanine nucleotide-binding protein G(i) subunit alpha
K04632  GNAS; guanine nucleotide-binding protein G(s) subunit alpha
K04633  GNAL; guanine nucleotide-binding protein G(olf) subunit alpha
K04634  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha
K04635  GNA11; guanine nucleotide-binding protein subunit alpha-11
K04805  CHRNA3; nicotinic acetylcholine receptor alpha-3
K04806  CHRNA4; nicotinic acetylcholine receptor alpha-4
K04808  CHRNA6; nicotinic acetylcholine receptor alpha-6
K04809  CHRNA7; nicotinic acetylcholine receptor alpha-7
K04813  CHRNB2; nicotinic acetylcholine receptor beta-2
K04815  CHRNB4; nicotinic acetylcholine receptor beta-4
K04819  HTR3; 5-hydroxytryptamine receptor 3
K05034  SLC6A1, GAT1; solute carrier family 6 (neurotransmitter transporter, GABA) member 1
K05035  SLC6A2, NET; solute carrier family 6 (neurotransmitter transporter, noradrenalin) member 2
K05036  SLC6A3, DAT; solute carrier family 6 (neurotransmitter transporter, dopamine) member 3
K05037  SLC6A4, SERT; solute carrier family 6 (neurotransmitter transporter, serotonin) member 4
K05038  SLC6A5_9, GLYT; solute carrier family 6 (neurotransmitter transporter, glycine) member 5/9
K05044  SLC6A11, GAT3; solute carrier family 6 (neurotransmitter transporter, GABA) member 11
K05045  SLC6A12, BGT1; solute carrier family 6 (neurotransmitter transporter, betaine/GABA) member 12
K05046  SLC6A13, GAT2; solute carrier family 6 (neurotransmitter transporter, GABA) member 13
K05175  GABRA; gamma-aminobutyric acid receptor subunit alpha
K05181  GABRB; gamma-aminobutyric acid receptor subunit beta
K05184  GABRD; gamma-aminobutyric acid receptor subunit delta
K05185  GABRE; gamma-aminobutyric acid receptor subunit epsilon
K05186  GABRG; gamma-aminobutyric acid receptor subunit gamma
K05189  GABRP; gamma-aminobutyric acid receptor subunit pi
K05190  GABRR; gamma-aminobutyric acid receptor subunit rho
K05192  GABRQ; gamma-aminobutyric acid receptor subunit theta
K05193  GLRA1; glycine receptor alpha-1
K05195  GLRA3; glycine receptor alpha-3
K05196  GLRB; glycine receptor beta
K05197  GRIA1; glutamate receptor 1
K05198  GRIA2; glutamate receptor 2
K05199  GRIA3; glutamate receptor 3
K05200  GRIA4; glutamate receptor 4
K05201  GRIK1; glutamate receptor, ionotropic kainate 1
K05202  GRIK2; glutamate receptor, ionotropic kainate 2
K05203  GRIK3; glutamate receptor, ionotropic kainate 3
K05204  GRIK4; glutamate receptor, ionotropic kainate 4
K05205  GRIK5; glutamate receptor, ionotropic kainate 5
K05208  GRIN1; glutamate receptor ionotropic, NMDA 1
K05209  GRIN2A; glutamate receptor ionotropic, NMDA 2A
K05210  GRIN2B; glutamate receptor ionotropic, NMDA 2B
K05211  GRIN2C; glutamate receptor ionotropic, NMDA 2C
K05212  GRIN2D; glutamate receptor ionotropic, NMDA 2D
K05213  GRIN3A; glutamate receptor ionotropic, NMDA 3A
K05214  GRIN3B; glutamate receptor ionotropic, NMDA 3B
K05215  P2RX1; P2X purinoceptor 1
K05216  P2RX2; P2X purinoceptor 2
K05217  P2RX3; P2X purinoceptor 3
K05218  P2RX4; P2X purinoceptor 4
K05219  P2RX5; P2X purinoceptor 5
K05221  P2RX6, P2RXL1; P2X purinoceptor 6
K05228  POMC; proopiomelanocortin
K05231  AGRP; agouti related protein
K05239  TAC1; tachykinin 1
K05240  TAC3; tachykinin 3
K05241  TAC4; tachykinin 4
K05612  SLC1A1, EAAT3; solute carrier family 1 (neuronal/epithelial high affinity glutamate transporter), member 1
K05613  SLC1A2, EAAT2; solute carrier family 1 (glial high affinity glutamate transporter), member 2
K05614  SLC1A3, EAAT1; solute carrier family 1 (glial high affinity glutamate transporter), member 3
K05617  SLC1A6, EAAT4; solute carrier family 1 (high affinity glutamate/aspartate transporter), member 6
K05618  SLC1A7, EAAT5; solute carrier family 1 (glutamate transporter), member 7
K05840  DRD5; dopamine receptor D5
K05858  PLCB; phosphatidylinositol phospholipase C, beta [EC:3.1.4.11]
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
K08041  ADCY1; adenylate cyclase 1 [EC:4.6.1.1]
K08042  ADCY2; adenylate cyclase 2 [EC:4.6.1.1]
K08043  ADCY3; adenylate cyclase 3 [EC:4.6.1.1]
K08044  ADCY4; adenylate cyclase 4 [EC:4.6.1.1]
K08045  ADCY5; adenylate cyclase 5 [EC:4.6.1.1]
K08046  ADCY6; adenylate cyclase 6 [EC:4.6.1.1]
K08047  ADCY7; adenylate cyclase 7 [EC:4.6.1.1]
K08048  ADCY8; adenylate cyclase 8 [EC:4.6.1.1]
K08049  ADCY9; adenylate cyclase 9 [EC:4.6.1.1]
K08155  SLC18A1_2, VMAT; MFS transporter, DHA1 family, solute carrier family 18 (vesicular amine transporter), member A1/2
K08387  P2RY11; P2Y purinoceptor 11
K08388  P2RY13; P2Y purinoceptor 13
K12302  SLC17A6_7_8; MFS transporter, ACS family, solute carrier family 17 (sodium-dependent inorganic phosphate cotransporter), member 6/7/8
K12303  SLC17A9; MFS transporter, ACS family, solute carrier family 17 (sodium-dependent inorganic phosphate cotransporter), member 9
K14387  SLC5A7, CHT1; solute carrier family 5 (high affinity choline transporter), member 7
K14636  SLC18A3, VACHT; MFS transporter, DHA1 family, solute carrier family 18 (vesicular acetylcholine transporter), member A3
K15015  SLC32A, VGAT; solute carrier family 32 (vesicular inhibitory amino acid transporter)
K15840  PDYN, PENKB; proenkephalin B (prodynorphin)
K18832  PENK; proenkephalin A
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]
K25696  PNOC; prepronociceptin
K27951  OGFR, OGFRL; opioid growth factor receptor
Compound
C00002  ATP
C00008  ADP
C00015  UDP
C00025  L-Glutamate
C00029  UDP-glucose
C00037  Glycine
C00075  UTP
C00076  Calcium cation
C00114  Choline
C00165  Diacylglycerol
C00212  Adenosine
C00334  4-Aminobutanoate
C00388  Histamine
C00547  L-Noradrenaline
C00575  3',5'-Cyclic AMP
C00698  Cl-
C00780  Serotonin
C00788  L-Adrenaline
C01330  Sodium cation
C01996  Acetylcholine
C02210  beta-Endorphin
C02758  alpha-Melanotropin
C03758  Dopamine
C11684  MET-enkephalin
C15871  Nocistatin
C16039  alpha-Neoendorphin
C16040  beta-Neoendorphin
C16041  Leu-enkephalin
C16044  Nociceptin
C16094  Substance P
C16095  Neuropeptide K
C16096  Neuropeptide gamma
C16097  Neurokinin A
C16098  Neurokinin B
C16099  Endokinin A/B
C16100  Endokinin C
C16101  Endokinin D
C16103  Agouti related protein (87-132)
C16136  beta-Melanotropin
C16137  gamma-Melanotropin
Reference
PMID:37385351
  Authors
Nimgampalle M, Chakravarthy H, Sharma S, Shree S, Bhat AR, Pradeepkiran JA, Devanathan V
  Title
Neurotransmitter systems in the etiology of major neurological disorders: Emerging insights and therapeutic implications.
  Journal
Ageing Res Rev 89:101994 (2023)
DOI:10.1016/j.arr.2023.101994
Reference
PMID:31726793
  Authors
Malik AR, Willnow TE
  Title
Excitatory Amino Acid Transporters in Physiology and Disorders of the Central Nervous System.
  Journal
Int J Mol Sci 20:ijms20225671 (2019)
DOI:10.3390/ijms20225671
Reference
PMID:25116141
  Authors
Higley MJ
  Title
Localized GABAergic inhibition of dendritic Ca(2+) signalling.
  Journal
Nat Rev Neurosci 15:567-72 (2014)
DOI:10.1038/nrn3803
Reference
PMID:12888801
  Authors
Brambilla P, Perez J, Barale F, Schettini G, Soares JC
  Title
GABAergic dysfunction in mood disorders.
  Journal
Mol Psychiatry 8:721-37, 715 (2003)
DOI:10.1038/sj.mp.4001362
Reference
PMID:35055019
  Authors
Shimizu-Okabe C, Kobayashi S, Kim J, Kosaka Y, Sunagawa M, Okabe A, Takayama C
  Title
Developmental Formation of the GABAergic and Glycinergic Networks in the Mouse Spinal Cord.
  Journal
Int J Mol Sci 23:ijms23020834 (2022)
DOI:10.3390/ijms23020834
Reference
PMID:33924731
  Authors
Wang Y, Tan B, Wang Y, Chen Z
  Title
Cholinergic Signaling, Neural Excitability, and Epilepsy.
  Journal
Molecules 26:molecules26082258 (2021)
DOI:10.3390/molecules26082258
Reference
PMID:36757901
  Authors
Channer B, Matt SM, Nickoloff-Bybel EA, Pappa V, Agarwal Y, Wickman J, Gaskill PJ
  Title
Dopamine, Immunity, and Disease.
  Journal
Pharmacol Rev 75:62-158 (2023)
DOI:10.1124/pharmrev.122.000618
Reference
PMID:25037203
  Authors
Savica R, Benarroch EE
  Title
Dopamine receptor signaling in the forebrain: recent insights and clinical implications.
  Journal
Neurology 83:758-67 (2014)
DOI:10.1212/WNL.0000000000000719
Reference
PMID:33651238
  Authors
Pourhamzeh M, Moravej FG, Arabi M, Shahriari E, Mehrabi S, Ward R, Ahadi R, Joghataei MT
  Title
The Roles of Serotonin in Neuropsychiatric Disorders.
  Journal
Cell Mol Neurobiol 42:1671-1692 (2022)
DOI:10.1007/s10571-021-01064-9
Reference
PMID:35492402
  Authors
Chhatar S, Lal G
  Title
Role of adrenergic receptor signalling in neuroimmune communication.
  Journal
Curr Res Immunol 2:202-217 (2021)
DOI:10.1016/j.crimmu.2021.11.001
Reference
PMID:39337347
  Authors
Szukiewicz D
  Title
Histaminergic System Activity in the Central Nervous System: The Role in Neurodevelopmental and Neurodegenerative Disorders.
  Journal
Int J Mol Sci 25:ijms25189859 (2024)
DOI:10.3390/ijms25189859
Reference
PMID:33907179
  Authors
Huang Z, Xie N, Illes P, Di Virgilio F, Ulrich H, Semyanov A, Verkhratsky A, Sperlagh B, Yu SG, Huang C, Tang Y
  Title
From purines to purinergic signalling: molecular functions and human diseases.
  Journal
Signal Transduct Target Ther 6:162 (2021)
DOI:10.1038/s41392-021-00553-z
Reference
PMID:16715052
  Authors
Fields RD, Burnstock G
  Title
Purinergic signalling in neuron-glia interactions.
  Journal
Nat Rev Neurosci 7:423-36 (2006)
DOI:10.1038/nrn1928
Reference
PMID:26880796
  Authors
Cawley NX, Li Z, Loh YP
  Title
60 YEARS OF POMC: Biosynthesis, trafficking, and secretion of pro-opiomelanocortin-derived peptides.
  Journal
J Mol Endocrinol 56:T77-97 (2016)
DOI:10.1530/JME-15-0323
Reference
PMID:28360832
  Authors
Butler AA, Girardet C, Mavrikaki M, Trevaskis JL, Macarthur H, Marks DL, Farr SA
  Title
A Life without Hunger: The Ups (and Downs) to Modulating Melanocortin-3 Receptor Signaling.
  Journal
Front Neurosci 11:128 (2017)
DOI:10.3389/fnins.2017.00128
Reference
PMID:26956246
  Authors
Toll L, Bruchas MR, Calo' G, Cox BM, Zaveri NT
  Title
Nociceptin/Orphanin FQ Receptor Structure, Signaling, Ligands, Functions, and Interactions with Opioid Systems.
  Journal
Pharmacol Rev 68:419-57 (2016)
DOI:10.1124/pr.114.009209
Reference
PMID:36589829
  Authors
Campo A, Dufour S, Rousseau K
  Title
Tachykinins, new players in the control of reproduction and food intake: A comparative review in mammals and teleosts.
  Journal
Front Endocrinol (Lausanne) 13:1056939 (2022)
DOI:10.3389/fendo.2022.1056939
Related
pathway
ko04080  Neuroactive ligand-receptor interaction
ko04724  Glutamatergic synapse
ko04725  Cholinergic synapse
ko04726  Serotonergic synapse
ko04727  GABAergic synapse
ko04728  Dopaminergic synapse

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