KEGG   PATHWAY: opi04725
Entry
opi04725                    Pathway                                
Name
Cholinergic synapse - Ochotona princeps (American pika)
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
opi04725  Cholinergic synapse
opi04725

Other DBs
GO: 0032222
Organism
Ochotona princeps (American pika) [GN:opi]
Gene
101517234  CHAT; choline O-acetyltransferase [KO:K00623] [EC:2.3.1.6]
101532376  ACHE; acetylcholinesterase isoform X1 [KO:K01049] [EC:3.1.1.7]
101531249  SLC18A3; vesicular acetylcholine transporter [KO:K14636]
101526608  CHRM1; muscarinic acetylcholine receptor M1 [KO:K04129]
101529171  CHRM3; muscarinic acetylcholine receptor M3 [KO:K04131]
101526778  CHRM5; muscarinic acetylcholine receptor M5 [KO:K04133]
101517012  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
101518174  GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
101524349  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
101524739  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
101529337  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
101520538  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X2 [KO:K05858] [EC:3.1.4.11]
101524859  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
101526097  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
101516441  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X2 [KO:K04960]
101523549  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
101523439  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
101534827  PRKCG; protein kinase C gamma type isoform X1 [KO:K19663] [EC:2.7.11.13]
101524765  KCNQ1; potassium voltage-gated channel subfamily KQT member 1 [KO:K04926]
101529364  KCNQ2; potassium voltage-gated channel subfamily KQT member 2 isoform X2 [KO:K04927]
101533875  KCNQ3; potassium voltage-gated channel subfamily KQT member 3 [KO:K04928]
101516930  KCNQ4; potassium voltage-gated channel subfamily KQT member 4 [KO:K04929]
101530090  KCNQ5; potassium voltage-gated channel subfamily KQT member 5 isoform X1 [KO:K04930]
101519705  KCNJ2; inward rectifier potassium channel 2 [KO:K04996]
101518036  KCNJ12; ATP-sensitive inward rectifier potassium channel 12 [KO:K05005]
101525442  KCNJ4; inward rectifier potassium channel 4 [KO:K04998]
101530239  KCNJ14; ATP-sensitive inward rectifier potassium channel 14 [KO:K05007]
101532237  CHRM2; muscarinic acetylcholine receptor M2 [KO:K04130]
101530695  CHRM4; muscarinic acetylcholine receptor M4 [KO:K04132]
101525340  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha [KO:K04630]
101516368  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
101531957  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
101524943  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
101525483  GNB1; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 [KO:K04536]
101529615  GNB2; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 [KO:K04537]
101536793  GNB3; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 isoform X1 [KO:K07825]
101530547  GNB4; guanine nucleotide-binding protein subunit beta-4 [KO:K04538]
101532346  GNB5; guanine nucleotide-binding protein subunit beta-5 [KO:K04539]
101528942  GNG2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 [KO:K07826]
101528746  GNG3; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3 [KO:K04540]
101531710  GNG4; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-4 [KO:K04541]
101521396  GNG5; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5 [KO:K04542]
101516538  GNG7; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7 [KO:K04543]
101516227  GNG8; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8 [KO:K04544]
101531323  GNG10; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10 [KO:K04545]
101531879  GNG11; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11 [KO:K04546]
101524512  GNG14; putative guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-14 [KO:K04347]
101519866  GNG12; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12 [KO:K04347]
101535404  GNG13; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-13 [KO:K04547]
101531647  GNGT1; guanine nucleotide-binding protein G(T) subunit gamma-T1 [KO:K04548]
101534148  GNGT2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-T2 [KO:K04549]
101532095  KCNJ3; G protein-activated inward rectifier potassium channel 1 isoform X1 [KO:K04997]
101525377  KCNJ6; G protein-activated inward rectifier potassium channel 2 [KO:K05000]
101534593  PIK3CG; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform [KO:K21289] [EC:2.7.1.153]
101520859  PIK3R5; phosphoinositide 3-kinase regulatory subunit 5 [KO:K21290]
101533770  PIK3R6; phosphoinositide 3-kinase regulatory subunit 6 [KO:K21290]
101531636  HRAS; GTPase HRas [KO:K02833]
101534080  KRAS; GTPase KRas isoform X1 [KO:K07827]
101524465  NRAS; GTPase NRas [KO:K07828]
101533612  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
101530701  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
101525427  mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
101526067  FOS; proto-oncogene c-Fos isoform X1 [KO:K04379]
101518087  CHRNA7; neuronal acetylcholine receptor subunit alpha-7 [KO:K04809]
101536091  CHRNA4; neuronal acetylcholine receptor subunit alpha-4 [KO:K04806]
101520921  CHRNB2; neuronal acetylcholine receptor subunit beta-2 [KO:K04813]
101529723  CHRNA3; neuronal acetylcholine receptor subunit alpha-3 isoform X1 [KO:K04805]
101525060  CHRNB4; neuronal acetylcholine receptor subunit beta-4 [KO:K04815]
101524736  CHRNA6; neuronal acetylcholine receptor subunit alpha-6 [KO:K04808]
101533323  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
101528674  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
101529277  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
101527552  ADCY4; adenylate cyclase type 4 isoform X2 [KO:K08044] [EC:4.6.1.1]
101526286  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
101528764  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
101519430  ADCY7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
101523667  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
101517485  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
101534210  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
101525119  cAMP-dependent protein kinase catalytic subunit alpha-like [KO:K04345] [EC:2.7.11.11]
101516221  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
101532574  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
101521567  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
101532689  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
101531761  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
101533371  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
101532921  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
101523446  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
101534608  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
101519593  calcium/calmodulin-dependent protein kinase type II subunit beta [KO:K04515] [EC:2.7.11.17]
101528216  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X11 [KO:K04515] [EC:2.7.11.17]
101524356  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X2 [KO:K04515] [EC:2.7.11.17]
101535936  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
101525109  CAMK4; calcium/calmodulin-dependent protein kinase type IV [KO:K05869] [EC:2.7.11.17]
101518245  JAK2; tyrosine-protein kinase JAK2 [KO:K04447] [EC:2.7.10.2]
101517134  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
101519449  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
101533851  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X3 [KO:K00922] [EC:2.7.1.153]
101533024  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
101532354  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
101517982  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
101528030  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
101533296  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
101519021  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
101525801  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101517543  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
101520695  CACNA1A; voltage-dependent P/Q-type calcium channel subunit alpha-1A isoform X3 [KO:K04344]
101523955  CACNA1B; voltage-dependent N-type calcium channel subunit alpha-1B [KO:K04849]
101536063  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
101524545  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
101519864  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853]
101529015  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
101528427  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
opi00564  Glycerophospholipid metabolism
opi04010  MAPK signaling pathway
opi04020  Calcium signaling pathway
opi04721  Synaptic vesicle cycle
opi04975  Fat digestion and absorption
KO pathway
ko04725   
LinkDB

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