KEGG   PATHWAY: rno04725
Entry
rno04725                    Pathway                                
Name
Cholinergic synapse - Rattus norvegicus (rat)
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
rno04725  Cholinergic synapse
rno04725

Other DBs
GO: 0032222
Organism
Rattus norvegicus (rat) [GN:rno]
Gene
290567  Chat; choline O-acetyltransferase [KO:K00623] [EC:2.3.1.6]
83817  Ache; acetylcholinesterase precursor [KO:K01049] [EC:3.1.1.7]
60422  Slc18a3; vesicular acetylcholine transporter [KO:K14636]
25229  Chrm1; muscarinic acetylcholine receptor M1 [KO:K04129]
24260  Chrm3; muscarinic acetylcholine receptor M3 [KO:K04131]
53949  Chrm5; muscarinic acetylcholine receptor M5 [KO:K04133]
81666  Gnaq; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
81662  Gna11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
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]
84020  Kcnq1; potassium voltage-gated channel subfamily KQT member 1 [KO:K04926]
170848  Kcnq2; potassium voltage-gated channel subfamily KQT member 2 [KO:K04927]
29682  Kcnq3; potassium voltage-gated channel subfamily KQT member 3 [KO:K04928]
298496  Kcnq4; potassium voltage-gated channel subfamily KQT member 4 [KO:K04929]
259273  Kcnq5; potassium voltage-gated channel subfamily KQT member 5 [KO:K04930]
29712  Kcnj2; inward rectifier potassium channel 2 [KO:K04996]
117052  Kcnj12; ATP-sensitive inward rectifier potassium channel 12 [KO:K05005]
116649  Kcnj4; inward rectifier potassium channel 4 [KO:K04998]
276720  Kcnj14; ATP-sensitive inward rectifier potassium channel 14 [KO:K05007]
81645  Chrm2; muscarinic acetylcholine receptor M2 [KO:K04130]
25111  Chrm4; muscarinic acetylcholine receptor M4 [KO:K04132]
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]
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]
298947  Pik3cg; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform [KO:K21289] [EC:2.7.1.153]
497931  Pik3r5; phosphoinositide 3-kinase regulatory subunit 5 [KO:K21290]
497932  Pik3r6; phosphoinositide 3-kinase regulatory subunit 6 [KO:K21290]
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]
170851  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
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]
314322  Fos; protein c-Fos [KO:K04379]
25302  Chrna7; neuronal acetylcholine receptor subunit alpha-7 precursor [KO:K04809]
25590  Chrna4; neuronal acetylcholine receptor subunit alpha-4 precursor [KO:K04806]
54239  Chrnb2; neuronal acetylcholine receptor subunit beta-2 precursor [KO:K04813]
25101  Chrna3; neuronal acetylcholine receptor subunit alpha-3 precursor [KO:K04805]
25103  Chrnb4; neuronal acetylcholine receptor subunit beta-4 precursor [KO:K04815]
81721  Chrna6; neuronal acetylcholine receptor subunit alpha-6 precursor [KO:K04808]
305509  Adcy1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
81636  Adcy2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
64508  Adcy3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
54223  Adcy4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
64532  Adcy5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
25289  Adcy6; adenylate cyclase type 6 isoform 2 [KO:K08046] [EC:4.6.1.1]
84420  Adcy7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
29241  Adcy8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
302950  Adcy9; adenylate cyclase type 9 [KO:K08049] [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]
81646  Creb1; cyclic AMP-responsive element-binding protein 1 isoform A [KO:K05870]
79255  Atf4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
310616  Creb3l4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform 1 [KO:K09048]
362165  Creb3l1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
362339  Creb3l2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
314638  Creb3l3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
500131  Creb5; cyclic AMP-responsive element-binding protein 5 [KO:K09047]
25400  Camk2a; calcium/calmodulin-dependent protein kinase type II subunit alpha [KO:K04515] [EC:2.7.11.17]
24246  Camk2d; calcium/calmodulin-dependent protein kinase type II subunit delta [KO:K04515] [EC:2.7.11.17]
24245  Camk2b; calcium/calmodulin-dependent protein kinase type II subunit beta isoform 2 [KO:K04515] [EC:2.7.11.17]
171140  Camk2g; calcium/calmodulin-dependent protein kinase type II subunit gamma [KO:K04515] [EC:2.7.11.17]
25050  Camk4; calcium/calmodulin-dependent protein kinase type IV [KO:K05869] [EC:2.7.11.17]
24514  Jak2; tyrosine-protein kinase JAK2 [KO:K04447] [EC:2.7.10.2]
25150  Fyn; tyrosine-protein kinase Fyn [KO:K05703] [EC:2.7.10.2]
85243  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
170911  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
366508  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
134484121  LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform-like [KO:K00922] [EC:2.7.1.153]
25513  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
60664  Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
29741  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
24185  Akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
25233  Akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
29414  Akt3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
24224  Bcl2; apoptosis regulator Bcl-2 [KO:K02161]
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]
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]
85426  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
rno00564  Glycerophospholipid metabolism
rno04010  MAPK signaling pathway
rno04020  Calcium signaling pathway
rno04721  Synaptic vesicle cycle
rno04975  Fat digestion and absorption
KO pathway
ko04725   
LinkDB

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