KEGG PATHWAY: ko04725

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

Disease

H00606	Early infantile epileptic encephalopathy
H00746	Hypokalemic periodic paralysis (HypoPP)
H00748	Andersen-Tawil syndrome (ATS)
H00749	Episodic ataxias
H00770	Congenital myasthenic syndrome
H00775	Familial or sporadic hemiplegic migraine
H00806	Benign familial neonatal and infantile epilepsies
H00807	Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE)

Drug

D00805	Metrifonate (USP/INN)
D03791	Dichlorvos (USAN/INN)

Other DBs

BSID:

217706

GO:

0032222

Orthology

K00623	choline O-acetyltransferase [EC:2.3.1.6]
K01049	acetylcholinesterase [EC:3.1.1.7]
K14636	MFS transporter, DHA1 family, solute carrier family 18 (vesicular acetylcholine transporter), member 3
K04129	muscarinic acetylcholine receptor M1
K04131	muscarinic acetylcholine receptor M3
K04133	muscarinic acetylcholine receptor M5
K04634	guanine nucleotide-binding protein G(q) subunit alpha
K04635	guanine nucleotide-binding protein subunit alpha-11
K05858	phosphatidylinositol phospholipase C, beta [EC:3.1.4.11]
K04958	inositol 1,4,5-triphosphate receptor type 1
K04959	inositol 1,4,5-triphosphate receptor type 2
K04960	inositol 1,4,5-triphosphate receptor type 3
K02677	classical protein kinase C [EC:2.7.11.13]
K04926	potassium voltage-gated channel KQT-like subfamily member 1
K04927	potassium voltage-gated channel KQT-like subfamily member 2
K04928	potassium voltage-gated channel KQT-like subfamily member 3
K04929	potassium voltage-gated channel KQT-like subfamily member 4
K04930	potassium voltage-gated channel KQT-like subfamily member 5
K04996	potassium inwardly-rectifying channel subfamily J member 2
K05005	potassium inwardly-rectifying channel subfamily J member 12
K04998	potassium inwardly-rectifying channel subfamily J member 4
K05007	potassium inwardly-rectifying channel subfamily J member 14
K04130	muscarinic acetylcholine receptor M2
K04132	muscarinic acetylcholine receptor M4
K04630	guanine nucleotide-binding protein G(i) subunit alpha
K04534	guanine nucleotide-binding protein G(o) subunit alpha
K04536	guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
K04537	guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2
K07825	guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3
K04538	guanine nucleotide-binding protein subunit beta-4
K04539	guanine nucleotide-binding protein subunit beta-5
K07826	guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
K04540	guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3
K04541	guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-4
K04542	guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5
K04543	guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7
K04544	guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8
K04545	guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10
K04546	guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11
K04347	guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12
K04547	guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-13
K04548	guanine nucleotide-binding protein G(T) subunit gamma-T1
K04549	guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-T2
K04997	potassium inwardly-rectifying channel subfamily J member 3
K05000	potassium inwardly-rectifying channel subfamily J member 6
K02833	GTPase HRas
K07827	GTPase KRas
K07828	GTPase NRas
K04368	mitogen-activated protein kinase kinase 1 [EC:2.7.12.2]
K04371	extracellular signal-regulated kinase 1/2 [EC:2.7.11.24]
K04379	proto-oncogene protein c-fos
K04809	nicotinic acetylcholine receptor alpha-7
K04806	nicotinic acetylcholine receptor alpha-4
K04813	nicotinic acetylcholine receptor beta-2
K04805	nicotinic acetylcholine receptor alpha-3
K04815	nicotinic acetylcholine receptor beta-4
K04808	nicotinic acetylcholine receptor alpha-6
K08041	adenylate cyclase 1 [EC:4.6.1.1]
K08042	adenylate cyclase 2 [EC:4.6.1.1]
K08043	adenylate cyclase 3 [EC:4.6.1.1]
K08044	adenylate cyclase 4 [EC:4.6.1.1]
K08045	adenylate cyclase 5 [EC:4.6.1.1]
K08046	adenylate cyclase 6 [EC:4.6.1.1]
K08047	adenylate cyclase 7 [EC:4.6.1.1]
K08048	adenylate cyclase 8 [EC:4.6.1.1]
K08049	adenylate cyclase 9 [EC:4.6.1.1]
K04345	protein kinase A [EC:2.7.11.11]
K05870	cyclic AMP-responsive element-binding protein 1
K04374	cyclic AMP-dependent transcription factor ATF-4
K09048	cyclic AMP-responsive element-binding protein 3
K09047	cyclic AMP-responsive element-binding protein 5
K04515	calcium/calmodulin-dependent protein kinase (CaM kinase) II [EC:2.7.11.17]
K05869	calcium/calmodulin-dependent protein kinase IV [EC:2.7.11.17]
K04447	Janus kinase 2 [EC:2.7.10.2]
K05703	tyrosine-protein kinase Fyn [EC:2.7.10.2]
K00922	phosphatidylinositol-4,5-bisphosphate 3-kinase [EC:2.7.1.153]
K02649	phosphoinositide-3-kinase, regulatory subunit
K04456	RAC serine/threonine-protein kinase [EC:2.7.11.1]
K02161	apoptosis regulator BCL-2
K04344	voltage-dependent calcium channel P/Q type alpha-1A
K04849	voltage-dependent calcium channel N type alpha-1B
K04850	voltage-dependent calcium channel L type alpha-1C
K04851	voltage-dependent calcium channel L type alpha-1D
K04853	voltage-dependent calcium channel L type alpha-1F
K04857	voltage-dependent calcium channel L type alpha-1S
K14387	solute carrier family 5 (high affinity choline transporter), member 7

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)

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)

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)

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)

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)

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)

Reference

PMID:11283752

Authors

Soreq H, Seidman S

Title

Acetylcholinesterase--new roles for an old actor.

Journal

Nat Rev Neurosci 2:294-302 (2001)

Reference

PMID:12436417

Authors

Sharma G, Vijayaraghavan S

Title

Nicotinic receptor signaling in nonexcitable cells.

Journal

J Neurobiol 53:524-34 (2002)

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)

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)

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)

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Ontology (2)   
   KEGG BRITE (1)   
   GO (1)   
Pathway (2)   
   KEGG PATHWAY (1)   
   BioSystems (1)   
Disease (8)   
   KEGG DISEASE (8)   
Drug (2)   
   KEGG DRUG (2)   
Chemical substance (12)   
   KEGG COMPOUND (12)   
Chemical reaction (12)   
   KEGG ENZYME (12)   
Gene (86)   
   KEGG ORTHOLOGY (86)   
Literature (12)   
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