KEGG   PATHWAY: rno04728
Entry
rno04728                    Pathway                                
Name
Dopaminergic synapse - Rattus norvegicus (rat)
Description
Dopamine (DA) is an important and prototypical slow neurotransmitter in the mammalian brain, where it controls a variety of functions including locomotor activity, motivation and reward, learning and memory, and endocrine regulation. Once released from presynaptic axonal terminals, DA interacts with at least five receptor subtypes in the central nervous system (CNS), which have been divided into two groups: the D1-like receptors (D1Rs), comprising D1 and D5 receptors, both positively coupled to adenylyl cyclase and cAMP production, and the D2-like receptors (D2Rs), comprising D2, D3, and D4 receptors, whose activation results in inhibition of adenylyl cyclase and suppression of cAMP production. In addition, D1Rs and D2Rs modulate intracellular Ca2+ levels and a number of Ca2+ -dependent intracellular signaling processes. Through diverse cAMP- and Ca2+-dependent and - independent mechanisms, DA influences neuronal activity, synaptic plasticity, and behavior. Presynaptically localized D2Rs regulate synthesis and release of DA as the main autoreceptor of the dopaminergic system.
Class
Organismal Systems; Nervous system
Pathway map
rno04728  Dopaminergic synapse
rno04728

Other DBs
GO: 0001963
Organism
Rattus norvegicus (rat) [GN:rno]
Gene
25085  Th; tyrosine 3-monooxygenase [KO:K00501] [EC:1.14.16.2]
24311  Ddc; aromatic-L-amino-acid decarboxylase isoform a [KO:K01593] [EC:4.1.1.28 4.1.1.105]
25549  Slc18a2; synaptic vesicular amine transporter [KO:K08155]
25693  Slc18a1; chromaffin granule amine transporter [KO:K08155]
24316  Drd1; D(1A) dopamine receptor [KO:K04144]
25195  Drd5; D(1B) dopamine receptor [KO:K05840]
192349  Caly; neuron-specific vesicular protein calcyon [KO:K15493]
81666  Gnaq; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
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]
364774  Calml5; calmodulin-like protein 5 [KO:K02183]
307100  Calml3; calmodulin-like protein 3 [KO:K02183]
691455  Calml4; calmodulin-like protein 4 [KO:K02183]
24242  Calm1; calmodulin-1 [KO:K02183]
24244  Calm3; calmodulin-3 [KO:K02183]
50663  Calm2; calmodulin-2 [KO:K02183]
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]
24674  Ppp3ca; protein phosphatase 3 catalytic subunit alpha [KO:K04348] [EC:3.1.3.16]
24675  Ppp3cb; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform [KO:K04348] [EC:3.1.3.16]
171378  Ppp3cc; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform [KO:K04348] [EC:3.1.3.16]
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]
314322  Fos; protein c-Fos [KO:K04379]
24896  Gnas; SCG6 (secretogranin VI) isoform SCG6 precursor [KO:K04632]
24611  Gnal; guanine nucleotide-binding protein G(olf) subunit alpha [KO:K04633]
64532  Adcy5; adenylate cyclase type 5 [KO:K08045] [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]
81647  Atf2; cyclic AMP-dependent transcription factor ATF-2 [KO:K04450]
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]
406169  Atf6b; cyclic AMP-dependent transcription factor ATF-6 beta [KO:K09049]
81649  Mapk14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
60352  Mapk12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
29513  Mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
689314  Mapk11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
25272  Mapk10; mitogen-activated protein kinase 10 isoform 2 [KO:K04440] [EC:2.7.11.24]
50658  Mapk9; mitogen-activated protein kinase 9 isoform 2 [KO:K04440] [EC:2.7.11.24]
116554  Mapk8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
360616  Ppp1r1b; protein phosphatase 1 regulatory subunit 1B [KO:K15494]
24668  Ppp1ca; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
24669  Ppp1cc; serine/threonine-protein phosphatase PP1-gamma catalytic subunit isoform 1 [KO:K06269] [EC:3.1.3.16]
25594  Ppp1cb; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
81574  Scn1a; sodium channel protein type 1 subunit alpha [KO:K04833]
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]
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]
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]
116560  Kcnj9; G protein-activated inward rectifier potassium channel 3 [KO:K05002]
29713  Kcnj5; G protein-activated inward rectifier potassium channel 4 [KO:K04999]
29238  Drd3; D(3) dopamine receptor [KO:K04146]
25432  Drd4; D(4) dopamine receptor [KO:K04147]
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]
24318  Drd2; D(2) dopamine receptor isoform 1 [KO:K04145]
25387  Arrb1; beta-arrestin-1 [KO:K04439]
25388  Arrb2; beta-arrestin-2 [KO:K04439]
24672  Ppp2ca; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
24673  Ppp2cb; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
100362453  Ppp2cal1; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform-like [KO:K04382] [EC:3.1.3.16]
117281  Ppp2r1a; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
315648  Ppp2r1b; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform [KO:K03456]
246255  Ppp2r2d; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform [KO:K04354]
60660  Ppp2r2b; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform 1 [KO:K04354]
117256  Ppp2r2c; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B gamma isoform isoform 1 [KO:K04354]
117104  Ppp2r2a; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform [KO:K04354]
682033  Ppp2r3b; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta [KO:K11583]
362739  Ppp2r3c; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma [KO:K11583]
363122  Ppp2r3a; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha [KO:K11583]
309179  Ppp2r5b; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
691318  Ppp2r5c; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform 4 [KO:K11584]
363193  Ppp2r5d; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
299147  Ppp2r5e; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform [KO:K11584]
312754  Ppp2r5a; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
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]
50686  Gsk3a; glycogen synthase kinase-3 alpha [KO:K08822] [EC:2.7.11.26]
84027  Gsk3b; glycogen synthase kinase-3 beta [KO:K03083] [EC:2.7.11.26]
24409  Grin2a; glutamate receptor ionotropic, NMDA 2A precursor [KO:K05209]
24410  Grin2b; glutamate receptor ionotropic, NMDA 2B precursor [KO:K05210]
50592  Gria1; glutamate receptor 1 precursor [KO:K05197]
29627  Gria2; glutamate receptor 2 isoform 2 precursor [KO:K05198]
29628  Gria3; glutamate receptor 3 isoform 2 precursor [KO:K05199]
29629  Gria4; glutamate receptor 4 isoform 2 precursor [KO:K05200]
117550  Kif5b; kinesin-1 heavy chain [KO:K10396]
311024  Kif5c; kinesin heavy chain isoform 5C [KO:K10396]
314906  Kif5a; kinesin heavy chain isoform 5A [KO:K10396]
60447  Clock; circadian locomoter output cycles protein kaput isoform 1 [KO:K02223] [EC:2.3.1.48]
29657  Bmal1; basic helix-loop-helix ARNT-like protein 1 [KO:K02296]
24898  Slc6a3; sodium-dependent dopamine transporter [KO:K05036]
25750  Maob; amine oxidase [flavin-containing] B [KO:K00274] [EC:1.4.3.4]
29253  Maoa; amine oxidase [flavin-containing] A [KO:K00274] [EC:1.4.3.4]
24267  Comt; catechol O-methyltransferase [KO:K00545] [EC:2.1.1.6]
308868  Lrtomt; transmembrane O-methyltransferase homolog [KO:K00545] [EC:2.1.1.6]
Compound
C00076  Calcium cation
C00082  L-Tyrosine
C00165  Diacylglycerol
C00238  Potassium cation
C00355  3,4-Dihydroxy-L-phenylalanine
C00575  3',5'-Cyclic AMP
C01161  3,4-Dihydroxyphenylacetate
C01245  D-myo-Inositol 1,4,5-trisphosphate
C01330  Sodium cation
C03758  Dopamine
C05582  Homovanillate
C05587  3-Methoxytyramine
Reference
PMID:21303898
  Authors
Beaulieu JM, Gainetdinov RR
  Title
The physiology, signaling, and pharmacology of dopamine receptors.
  Journal
Pharmacol Rev 63:182-217 (2011)
DOI:10.1124/pr.110.002642
Reference
PMID:15521361
  Authors
Neve KA, Seamans JK, Trantham-Davidson H
  Title
Dopamine receptor signaling.
  Journal
J Recept Signal Transduct Res 24:165-205 (2004)
DOI:10.1081/RRS-200029981
Reference
PMID:17408758
  Authors
Surmeier DJ, Ding J, Day M, Wang Z, Shen W
  Title
D1 and D2 dopamine-receptor modulation of striatal glutamatergic signaling in striatal medium spiny neurons.
  Journal
Trends Neurosci 30:228-35 (2007)
DOI:10.1016/j.tins.2007.03.008
Reference
PMID:20224735
  Authors
Knab AM, Lightfoot JT
  Title
Does the difference between physically active and couch potato lie in the dopamine system?
  Journal
Int J Biol Sci 6:133-50 (2010)
DOI:10.7150/ijbs.6.133
Reference
PMID:10433257
  Authors
Greengard P, Allen PB, Nairn AC
  Title
Beyond the dopamine receptor: the DARPP-32/protein phosphatase-1 cascade.
  Journal
Neuron 23:435-47 (1999)
DOI:10.1016/S0896-6273(00)80798-9
Reference
PMID:15590733
  Authors
Hu XT, Dong Y, Zhang XF, White FJ
  Title
Dopamine D2 receptor-activated Ca2+ signaling modulates voltage-sensitive sodium currents in rat nucleus accumbens neurons.
  Journal
J Neurophysiol 93:1406-17 (2005)
DOI:10.1152/jn.00771.2004
Reference
PMID:17349698
  Authors
Beaulieu JM, Gainetdinov RR, Caron MG
  Title
The Akt-GSK-3 signaling cascade in the actions of dopamine.
  Journal
Trends Pharmacol Sci 28:166-72 (2007)
DOI:10.1016/j.tips.2007.02.006
Reference
PMID:19138563
  Authors
De Mei C, Ramos M, Iitaka C, Borrelli E
  Title
Getting specialized: presynaptic and postsynaptic dopamine D2 receptors.
  Journal
Curr Opin Pharmacol 9:53-8 (2009)
DOI:10.1016/j.coph.2008.12.002
Reference
PMID:15381316
  Authors
Seamans JK, Yang CR
  Title
The principal features and mechanisms of dopamine modulation in the prefrontal cortex.
  Journal
Prog Neurobiol 74:1-58 (2004)
DOI:10.1016/j.pneurobio.2004.05.006
Reference
PMID:18353279
  Authors
Yao WD, Spealman RD, Zhang J
  Title
Dopaminergic signaling in dendritic spines.
  Journal
Biochem Pharmacol 75:2055-69 (2008)
DOI:10.1016/j.bcp.2008.01.018
Reference
PMID:20727368
  Authors
Li YC, Gao WJ
  Title
GSK-3beta activity and hyperdopamine-dependent behaviors.
  Journal
Neurosci Biobehav Rev 35:645-54 (2011)
DOI:10.1016/j.neubiorev.2010.08.001
Reference
PMID:15292232
  Authors
Tang TS, Bezprozvanny I
  Title
Dopamine receptor-mediated Ca(2+) signaling in striatal medium spiny neurons.
  Journal
J Biol Chem 279:42082-94 (2004)
DOI:10.1074/jbc.M407389200
Reference
PMID:12967774
  Authors
Bergson C, Levenson R, Goldman-Rakic PS, Lidow MS
  Title
Dopamine receptor-interacting proteins: the Ca(2+) connection in dopamine signaling.
  Journal
Trends Pharmacol Sci 24:486-92 (2003)
DOI:10.1016/S0165-6147(03)00232-3
Reference
PMID:9457173
  Authors
Missale C, Nash SR, Robinson SW, Jaber M, Caron MG
  Title
Dopamine receptors: from structure to function.
  Journal
Physiol Rev 78:189-225 (1998)
DOI:10.1152/physrev.1998.78.1.189
Reference
PMID:19251795
  Authors
Quaak M, van Schayck CP, Knaapen AM, van Schooten FJ
  Title
Genetic variation as a predictor of smoking cessation success. A promising preventive and intervention tool for chronic respiratory diseases?
  Journal
Eur Respir J 33:468-80 (2009)
DOI:10.1183/09031936.00056908
Related
pathway
rno00350  Tyrosine metabolism
rno04020  Calcium signaling pathway
rno04721  Synaptic vesicle cycle
rno04724  Glutamatergic synapse
rno05012  Parkinson disease
KO pathway
ko04728   
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