KEGG   PATHWAY: ko04725
Entry
ko04725                     Pathway                                
Name
Cholinergic synapse
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
ko04725  Cholinergic synapse
ko04725

Drug
D00805  Metrifonate (USP/INN)
D03791  Dichlorvos (USAN/INN)
D05076  Morantel tartrate (USP)
D06062  Temefos (USAN/INN)
D07479  Azamethiphos (BAN)
D07688  Chlorpyrifos (BAN)
D07722  Clofenvinfos (INN)
D07750  Coumafos (INN)
D07856  Dimpylate (INN)
D07950  Fenthion (BAN)
D08230  Morantel (BAN)
D08231  Morantel citrate
Other DBs
GO: 0032222
Orthology
K00623  CHAT; choline O-acetyltransferase [EC:2.3.1.6]
K00922  PIK3CA_B_D; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153]
K01049  ACHE; acetylcholinesterase [EC:3.1.1.7]
K02161  BCL2; apoptosis regulator Bcl-2
K02649  PIK3R1_2_3; phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K02677  PRKCA; classical protein kinase C alpha type [EC:2.7.11.13]
K02833  HRAS; GTPase HRas
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
K04344  CACNA1A, CAV2.1; voltage-dependent calcium channel P/Q type alpha-1A
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
K04368  MAP2K1, MEK1; mitogen-activated protein kinase kinase 1 [EC:2.7.12.2]
K04371  ERK, MAPK1_3; mitogen-activated protein kinase 1/3 [EC:2.7.11.24]
K04374  ATF4, CREB2; cyclic AMP-dependent transcription factor ATF-4
K04379  FOS; proto-oncogene protein c-fos
K04447  JAK2; Janus kinase 2 [EC:2.7.10.2]
K04456  AKT; RAC serine/threonine-protein kinase [EC:2.7.11.1]
K04515  CAMK2; calcium/calmodulin-dependent protein kinase (CaM kinase) II [EC:2.7.11.17]
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
K04630  GNAI; guanine nucleotide-binding protein G(i) 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
K04849  CACNA1B, CAV2.2; voltage-dependent calcium channel N type alpha-1B
K04850  CACNA1C, CAV1.2; voltage-dependent calcium channel L type alpha-1C
K04851  CACNA1D, CAV1.3; voltage-dependent calcium channel L type alpha-1D
K04853  CACNA1F, CAV1.4; voltage-dependent calcium channel L type alpha-1F
K04857  CACNA1S, CAV1.1; voltage-dependent calcium channel L type alpha-1S
K04926  KCNQ1, KV7.1; potassium voltage-gated channel KQT-like subfamily member 1
K04927  KCNQ2, KV7.2; potassium voltage-gated channel KQT-like subfamily member 2
K04928  KCNQ3, KV7.3; potassium voltage-gated channel KQT-like subfamily member 3
K04929  KCNQ4, KV7.4; potassium voltage-gated channel KQT-like subfamily member 4
K04930  KCNQ5, KV7.5; potassium voltage-gated channel KQT-like subfamily member 5
K04958  ITPR1; inositol 1,4,5-triphosphate receptor type 1
K04959  ITPR2; inositol 1,4,5-triphosphate receptor type 2
K04960  ITPR3; inositol 1,4,5-triphosphate receptor type 3
K04996  KCNJ2, KIR2.1; potassium inwardly-rectifying channel subfamily J member 2
K04997  KCNJ3, KIR3.1; potassium inwardly-rectifying channel subfamily J member 3
K04998  KCNJ4, KIR2.3; potassium inwardly-rectifying channel subfamily J member 4
K05000  KCNJ6, KIR3.2; potassium inwardly-rectifying channel subfamily J member 6
K05005  KCNJ12_18, KIR2.2, KIR2.6; potassium inwardly-rectifying channel subfamily J member 12/18
K05007  KCNJ14, KIR2.4; potassium inwardly-rectifying channel subfamily J member 14
K05703  FYN; tyrosine-protein kinase Fyn [EC:2.7.10.2]
K05858  PLCB; phosphatidylinositol phospholipase C, beta [EC:3.1.4.11]
K05869  CAMK4; calcium/calmodulin-dependent protein kinase IV [EC:2.7.11.17]
K05870  CREB1; cyclic AMP-responsive element-binding protein 1
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
K07827  KRAS, KRAS2; GTPase KRas
K07828  NRAS; GTPase NRas
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]
K09047  CREB5, CREBPA; cyclic AMP-responsive element-binding protein 5
K09048  CREB3; cyclic AMP-responsive element-binding protein 3
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 3
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]
K21289  PIK3CG; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma [EC:2.7.1.153]
K21290  PIK3R5_6; phosphoinositide-3-kinase regulatory subunit 5/6
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
ko00564  Glycerophospholipid metabolism
ko04010  MAPK signaling pathway
ko04020  Calcium signaling pathway
ko04721  Synaptic vesicle cycle
ko04975  Fat digestion and absorption

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