KEGG   PATHWAY: npo04725
Entry
npo04725                    Pathway                                
Name
Cholinergic synapse - Nyctereutes procyonoides (raccoon dog)
Description
Acetylcholine (ACh) is a neurotransmitter widely distributed in the central (and also peripheral, autonomic and enteric) nervous system (CNS). In the CNS, ACh facilitates many functions, such as learning, memory, attention and motor control. When released in the synaptic cleft, ACh binds to two distinct types of receptors: Ionotropic nicotinic acetylcholine receptors (nAChR) and metabotropic muscarinic acetylcholine receptors (mAChRs). The activation of nAChR by ACh leads to the rapid influx of Na+ and Ca2+ and subsequent cellular depolarization. Activation of mAChRs is relatively slow (milliseconds to seconds) and, depending on the subtypes present (M1-M5), they directly alter cellular homeostasis of phospholipase C, inositol trisphosphate, cAMP, and free calcium. In the cleft, ACh may also be hydrolyzed by acetylcholinesterase (AChE) into choline and acetate. The choline derived from ACh hydrolysis is recovered by a presynaptic high-affinity choline transporter (CHT).
Class
Organismal Systems; Nervous system
Pathway map
npo04725  Cholinergic synapse
npo04725

Other DBs
GO: 0032222
Organism
Nyctereutes procyonoides (raccoon dog) [GN:npo]
Gene
129523001  CHAT; choline O-acetyltransferase [KO:K00623] [EC:2.3.1.6]
129519694  ACHE; acetylcholinesterase isoform X1 [KO:K01049] [EC:3.1.1.7]
129522794  SLC18A3; vesicular acetylcholine transporter [KO:K14636]
129499185  CHRM1; muscarinic acetylcholine receptor M1 [KO:K04129]
129499244  CHRM3; muscarinic acetylcholine receptor M3 [KO:K04131]
129504266  CHRM5; muscarinic acetylcholine receptor M5 [KO:K04133]
129500644  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
129522061  GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
129496894  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
129504276  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
129497646  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
129500550  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
129521608  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
129505465  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
129512495  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
129494612  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
129519978  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
129500385  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
129502588  KCNQ1; potassium voltage-gated channel subfamily KQT member 1 [KO:K04926]
129521521  KCNQ2; potassium voltage-gated channel subfamily KQT member 2 isoform X1 [KO:K04927]
129502517  KCNQ3; potassium voltage-gated channel subfamily KQT member 3 [KO:K04928]
129520851  KCNQ4; potassium voltage-gated channel subfamily KQT member 4 isoform X1 [KO:K04929]
129513155  KCNQ5; potassium voltage-gated channel subfamily KQT member 5 isoform X1 [KO:K04930]
129517232  KCNJ2; inward rectifier potassium channel 2 [KO:K04996]
129497584  KCNJ12; ATP-sensitive inward rectifier potassium channel 12 [KO:K05005]
129512022  KCNJ4; inward rectifier potassium channel 4 [KO:K04998]
129500159  KCNJ14; ATP-sensitive inward rectifier potassium channel 14 [KO:K05007]
129515649  CHRM2; muscarinic acetylcholine receptor M2 [KO:K04130]
129500068  CHRM4; muscarinic acetylcholine receptor M4 [KO:K04132]
129494269  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
129519569  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630]
129522106  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
129513852  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
129497735  GNB1; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 [KO:K04536]
129520313  GNB2; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 [KO:K04537]
129503454  GNB3; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 [KO:K07825]
129498348  GNB4; guanine nucleotide-binding protein subunit beta-4 [KO:K04538]
129506463  GNB5; guanine nucleotide-binding protein subunit beta-5 isoform X1 [KO:K04539]
129496421  GNG2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 [KO:K07826]
129501173  GNG3; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3 [KO:K04540]
129499161  GNG4; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-4 isoform X1 [KO:K04541]
129520219  GNG5; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5 [KO:K04542]
129520847  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5-like [KO:K04542]
129522362  GNG7; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7 [KO:K04543]
129499702  GNG8; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8 [KO:K04544]
129494664  GNG10; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10 [KO:K04545]
129498223  GNG11; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11 [KO:K04546]
129519244  GNG12; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12 [KO:K04347]
129521436  GNG14; putative guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-14 [KO:K04347]
129519415  GNG13; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-13 [KO:K04547]
129498294  GNGT1; guanine nucleotide-binding protein G(T) subunit gamma-T1 [KO:K04548]
129512848  GNGT2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-T2 [KO:K04549]
129498792  KCNJ3; G protein-activated inward rectifier potassium channel 1 isoform X1 [KO:K04997]
129501980  KCNJ6; G protein-activated inward rectifier potassium channel 2 isoform X1 [KO:K05000]
129494039  PIK3CG; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform [KO:K21289] [EC:2.7.1.153]
129496567  PIK3R6; phosphoinositide 3-kinase regulatory subunit 6 isoform X1 [KO:K21290]
129497926  PIK3R5; phosphoinositide 3-kinase regulatory subunit 5 isoform X1 [KO:K21290]
129494224  HRAS; GTPase HRas isoform X1 [KO:K02833]
129505561  KRAS; GTPase KRas isoform X1 [KO:K07827]
129501466  NRAS; GTPase NRas [KO:K07828]
129506345  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
129502349  mitogen-activated protein kinase 3-like [KO:K04371] [EC:2.7.11.24]
129507918  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
129519082  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
129496401  FOS; protein c-Fos [KO:K04379]
129510377  neuronal acetylcholine receptor subunit alpha-7 isoform X1 [KO:K04809]
129496290  CHRNA4; neuronal acetylcholine receptor subunit alpha-4 [KO:K04806]
129509121  CHRNB2; neuronal acetylcholine receptor subunit beta-2 [KO:K04813]
129520705  CHRNA3; neuronal acetylcholine receptor subunit alpha-3 [KO:K04805]
129520248  CHRNB4; neuronal acetylcholine receptor subunit beta-4 [KO:K04815]
129516013  CHRNA6; neuronal acetylcholine receptor subunit alpha-6 isoform X1 [KO:K04808]
129515724  LOW QUALITY PROTEIN: adenylate cyclase type 1-like [KO:K08041] [EC:4.6.1.1]
129516202  adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
129498939  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
129510932  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
129499511  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
129503910  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
129517234  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
129513386  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
129502672  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
129519450  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
129519960  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
129521768  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
129522997  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
129518269  cyclic AMP-responsive element-binding protein 1-like [KO:K05870]
129511576  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
129508719  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
129494799  CREB3; cyclic AMP-responsive element-binding protein 3 isoform X1 [KO:K09048]
129503105  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
129515926  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
129522278  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
129502771  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
129515997  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
129509461  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
129509507  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
129521159  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
129503274  CAMK4; calcium/calmodulin-dependent protein kinase type IV [KO:K05869] [EC:2.7.11.17]
129499911  JAK2; tyrosine-protein kinase JAK2 [KO:K04447] [EC:2.7.10.2]
129513108  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
129496789  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
129498637  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
129507069  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
129513452  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
129520803  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
129522073  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
129508823  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
129495892  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
129499851  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
129517633  RAC-alpha serine/threonine-protein kinase-like [KO:K04456] [EC:2.7.11.1]
129514778  RAC-alpha serine/threonine-protein kinase-like [KO:K04456] [EC:2.7.11.1]
129495480  apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
129514527  apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
129522364  CACNA1A; voltage-dependent P/Q-type calcium channel subunit alpha-1A isoform X1 [KO:K04344]
129515558  CACNA1B; voltage-dependent N-type calcium channel subunit alpha-1B [KO:K04849]
129503382  CACNA1C; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1C [KO:K04850]
129521343  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851]
129517804  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853]
129505985  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
129512058  SLC5A7; high affinity choline transporter 1 [KO:K14387]
Compound
C00010  CoA
C00024  Acetyl-CoA
C00033  Acetate
C00076  Calcium cation
C00114  Choline
C00165  Diacylglycerol
C00238  Potassium cation
C00575  3',5'-Cyclic AMP
C01245  D-myo-Inositol 1,4,5-trisphosphate
C01330  Sodium cation
C01996  Acetylcholine
C04637  1-Phosphatidyl-D-myo-inositol 4,5-bisphosphate
Reference
  Authors
Nestler EJ, Hyman SE, Malenka RC.
  Title
Molecular neuropharmacology: A foundation for clinical neuroscience
  Journal
The McGraw-Hill Companies, Inc. (2001)
Reference
  Authors
Nicholls JG, Martin AR, Wallace BG, Fuchs PA.
  Title
From neuron to brain, 4th ed.
  Journal
Sunderland, MA: Sinauer associates (2001)
Reference
PMID:15165747
  Authors
Dajas-Bailador F, Wonnacott S
  Title
Nicotinic acetylcholine receptors and the regulation of neuronal signalling.
  Journal
Trends Pharmacol Sci 25:317-24 (2004)
DOI:10.1016/j.tips.2004.04.006
Reference
PMID:19712465
  Authors
Resende RR, Adhikari A
  Title
Cholinergic receptor pathways involved in apoptosis, cell proliferation and neuronal differentiation.
  Journal
Cell Commun Signal 7:20 (2009)
DOI:10.1186/1478-811X-7-20
Reference
PMID:19378880
  Authors
Origlia N, Kuczewski N, Pesavento E, Aztiria E, Domenici L
  Title
The role of cholinergic system in neuronal plasticity: focus on visual cortex and muscarinic receptors.
  Journal
Arch Ital Biol 146:165-88 (2008)
Reference
PMID:21550798
  Authors
Oldenburg IA, Ding JB
  Title
Cholinergic modulation of synaptic integration and dendritic excitability in the striatum.
  Journal
Curr Opin Neurobiol 21:425-32 (2011)
DOI:10.1016/j.conb.2011.04.004
Reference
PMID:12893537
  Authors
Lanzafame AA, Christopoulos A, Mitchelson F
  Title
Cellular signaling mechanisms for muscarinic acetylcholine receptors.
  Journal
Receptors Channels 9:241-60 (2003)
DOI:10.3109/10606820308263
Reference
PMID:20446119
  Authors
Brown DA
  Title
Muscarinic acetylcholine receptors (mAChRs) in the nervous system: some functions and mechanisms.
  Journal
J Mol Neurosci 41:340-6 (2010)
DOI:10.1007/s12031-010-9377-2
Reference
PMID:11738031
  Authors
Chang KT, Berg DK
  Title
Voltage-gated channels block nicotinic regulation of CREB phosphorylation and gene expression in neurons.
  Journal
Neuron 32:855-65 (2001)
DOI:10.1016/S0896-6273(01)00516-5
Reference
PMID:11283752
  Authors
Soreq H, Seidman S
  Title
Acetylcholinesterase--new roles for an old actor.
  Journal
Nat Rev Neurosci 2:294-302 (2001)
DOI:10.1038/35067589
Reference
PMID:12436417
  Authors
Sharma G, Vijayaraghavan S
  Title
Nicotinic receptor signaling in nonexcitable cells.
  Journal
J Neurobiol 53:524-34 (2002)
DOI:10.1002/neu.10114
Reference
PMID:11923408
  Authors
Araque A, Martin ED, Perea G, Arellano JI, Buno W
  Title
Synaptically released acetylcholine evokes Ca2+ elevations in astrocytes in hippocampal slices.
  Journal
J Neurosci 22:2443-50 (2002)
DOI:10.1523/JNEUROSCI.22-07-02443.2002
Reference
PMID:12690458
  Authors
Lucas-Meunier E, Fossier P, Baux G, Amar M
  Title
Cholinergic modulation of the cortical neuronal network.
  Journal
Pflugers Arch 446:17-29 (2003)
DOI:10.1007/s00424-002-0999-2
Reference
PMID:20060019
  Authors
Abreu-Villaca Y, Filgueiras CC, Manhaes AC
  Title
Developmental aspects of the cholinergic system.
  Journal
Behav Brain Res 221:367-78 (2011)
DOI:10.1016/j.bbr.2009.12.049
Related
pathway
npo00564  Glycerophospholipid metabolism
npo04010  MAPK signaling pathway
npo04020  Calcium signaling pathway
npo04721  Synaptic vesicle cycle
npo04975  Fat digestion and absorption
KO pathway
ko04725   
LinkDB

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