BioModels Database

Transient changes in striatal dopamine (DA) concentration are considered to encode a reward prediction error (RPE) in reinforcement learning tasks. Often, a phasic DA change occurs concomitantly with a dip in striatal acetylcholine (ACh), whereas other neuromodulators, such as adenosine (Adn), change slowly. There are abundant adenylyl cyclase (AC) coupled GPCRs for these neuromodulators in striatal medium spiny neurons (MSNs), which play important roles in plasticity. However, little is known about the interaction between these neuromodulators via GPCRs. The interaction between these transient neuromodulator changes and the effect on cAMP/PKA signaling via Golf- and Gi/o-coupled GPCR are studied here using quantitative kinetic modeling. The simulations suggest that, under basal conditions, cAMP/PKA signaling could be significantly inhibited in D1R+ MSNs via ACh/M4R/Gi/o and an ACh dip is required to gate a subset of D1R/Golf-dependent PKA activation. Furthermore, the interaction between ACh dip and DA peak, via D1R and M4R, is synergistic. In a similar fashion, PKA signaling in D2+ MSNs is under basal inhibition via D2R/Gi/o and a DA dip leads to a PKA increase by disinhibiting A2aR/Golf, but D2+ MSNs could also respond to the DA peak via other intracellular pathways. This study highlights the similarity between the two types of MSNs in terms of high basal AC inhibition by Gi/o and the importance of interactions between Gi/o and Golf signaling, but at the same time predicts differences between them with regard to the sign of RPE responsible for PKA activation.Dopamine transients are considered to carry reward-related signal in reinforcement learning. An increase in dopamine concentration is associated with an unexpected reward or salient stimuli, whereas a decrease is produced by omission of an expected reward. Often dopamine transients are accompanied by other neuromodulatory signals, such as acetylcholine and adenosine. We highlight the importance of interaction between acetylcholine, dopamine, and adenosine signals via adenylyl-cyclase coupled GPCRs in shaping the dopamine-dependent cAMP/PKA signaling in striatal neurons. Specifically, a dopamine peak and an acetylcholine dip must interact, via D1 and M4 receptor, and a dopamine dip must interact with adenosine tone, via D2 and A2a receptor, in direct and indirect pathway neurons, respectively, to have any significant downstream PKA activation.

Reactions (113)

revreaction_1

[D1RGolf] + [DA] ↔ [D1RDAGolf];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:isVersionOf

Reactome R-MMU-390835
Gene Ontology G-protein coupled receptor binding

revreaction_2

[D1RDA] + [Golf] ↔ [D1RDAGolf];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:isVersionOf

Gene Ontology heterotrimeric G-protein binding
Gene Ontology dopamine receptor signaling pathway

revreaction_3

[D1R] + [Golf] ↔ [D1RGolf];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:isVersionOf

Gene Ontology heterotrimeric G-protein binding
Gene Ontology D1 dopamine receptor binding

revreaction_4

[D1R] + [DA] ↔ [D1RDA];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:is

Reactome R-MMU-390835

revreaction_5

[M4R] + [Gi] ↔ [M4RGi];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:isVersionOf

Gene Ontology heterotrimeric G-protein binding
Gene Ontology acetylcholine receptor binding

revreaction_6

[M4RACh] + [Gi] ↔ [M4RAChGi];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:isVersionOf

Reactome R-MMU-749456
Gene Ontology G-protein coupled acetylcholine receptor activity
Gene Ontology heterotrimeric G-protein binding

revreaction_7

[ACh] + [M4RGi] ↔ [M4RAChGi];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:is

Gene Ontology G-protein coupled acetylcholine receptor binding

revreaction_8

[ACh] + [M4R] ↔ [M4RACh];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:is

Reactome R-MMU-390673

revreaction_9

[AC5] + [GaolfGTP] ↔ [AC5GaolfGTP];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:is

Reactome R-MMU-170672

revreaction_10

[AC5] + [Ca] ↔ [AC5Ca];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:hasPart

Gene Ontology calcium ion binding
Gene Ontology adenylate cyclase binding

revreaction_11

[AC5Ca] + [GaolfGTP] ↔ [AC5CaGaolfGTP];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:isVersionOf

Gene Ontology adenylate cyclase-activating G-protein coupled receptor signaling pathway

revreaction_12

[GaiGTP] + [AC5Ca] ↔ [AC5CaGaiGTP];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:isVersionOf

Gene Ontology adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway

revreaction_13

[GaiGTP] + [AC5] ↔ [AC5GaiGTP];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:isVersionOf

Gene Ontology adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway

revreaction_14

[GaiGTP] + [AC5GaolfGTP] ↔ [AC5GaolfGTPGaiGTP];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:hasPart

Gene Ontology adenylate cyclase-activating G-protein coupled receptor signaling pathway
Gene Ontology adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway

revreaction_15

[GaiGTP] + [AC5CaGaolfGTP] ↔ [AC5CaGaolfGTPGaiGTP];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:hasPart

Gene Ontology adenylate cyclase-activating G-protein coupled receptor signaling pathway
Gene Ontology adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway

revreaction_16

[AC5GaiGTP] + [GaolfGTP] ↔ [AC5GaolfGTPGaiGTP];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:hasPart

Gene Ontology adenylate cyclase-activating G-protein coupled receptor signaling pathway
Gene Ontology adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway

revreaction_17

[AC5CaGaiGTP] + [GaolfGTP] ↔ [AC5CaGaolfGTPGaiGTP];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:hasPart

Gene Ontology adenylate cyclase-activating G-protein coupled receptor signaling pathway
Gene Ontology adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway

revreaction_18

[AC5GaolfGTPGaiGTP] + [ATP] ↔ [AC5GaolfGTPGaiGTP*ATP];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:hasPart

Gene Ontology ATP binding
Gene Ontology adenylate cyclase-activating G-protein coupled receptor signaling pathway
Gene Ontology adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway

revreaction_19

[ATP] + [AC5GaiGTP] ↔ [AC5GaiGTP*ATP];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:hasPart	Gene Ontology ATP binding
bqbiol:isVersionOf	Gene Ontology adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway

revreaction_20

[AC5GaolfGTP] + [ATP] ↔ [AC5GaolfGTP*ATP];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:hasPart	Gene Ontology ATP binding
bqbiol:isVersionOf	Gene Ontology adenylate cyclase-activating G-protein coupled receptor signaling pathway

revreaction_21

[AC5] + [ATP] ↔ [AC5*ATP];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:hasPart

Gene Ontology adenylate cyclase binding
Gene Ontology ATP binding

revreaction_22

[AC5Ca] + [ATP] ↔ [AC5Ca*ATP];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:hasPart

Gene Ontology adenylate cyclase binding
Gene Ontology ATP binding

revreaction_23

[AC5CaGaolfGTP] + [ATP] ↔ [AC5CaGaolfGTP*ATP];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:hasPart	Gene Ontology ATP binding
bqbiol:isVersionOf	Gene Ontology adenylate cyclase-activating G-protein coupled receptor signaling pathway

revreaction_24

[AC5CaGaiGTP] + [ATP] ↔ [AC5CaGaiGTP*ATP];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:hasPart	Gene Ontology ATP binding
bqbiol:isVersionOf	Gene Ontology adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway

revreaction_25

[AC5CaGaolfGTPGaiGTP] + [ATP] ↔ [AC5CaGaolfGTPGaiGTP*ATP];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:hasPart

revreaction_26

[GaolfGTP] + [AC5GaiGTP*ATP] ↔ [AC5GaolfGTPGaiGTP*ATP];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:hasPart

Gene Ontology adenylate cyclase-activating G-protein coupled receptor signaling pathway
Gene Ontology adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway

revreaction_27

[GaolfGTP] + [AC5CaGaiGTP*ATP] ↔ [AC5CaGaolfGTPGaiGTP*ATP];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:hasPart

Gene Ontology adenylate cyclase-activating G-protein coupled receptor signaling pathway
Gene Ontology adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway

revreaction_28

[GaolfGTP] + [AC5*ATP] ↔ [AC5GaolfGTP*ATP];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:isVersionOf

Gene Ontology adenylate cyclase-activating G-protein coupled receptor signaling pathway

revreaction_29

[GaolfGTP] + [AC5Ca*ATP] ↔ [AC5CaGaolfGTP*ATP];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:isVersionOf

Gene Ontology adenylate cyclase-activating G-protein coupled receptor signaling pathway

revreaction_30

[Ca] + [AC5*ATP] ↔ [AC5Ca*ATP];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:hasPart

Gene Ontology calcium ion binding
Gene Ontology adenylate cyclase binding

revreaction_31

[AC5*ATP] + [GaiGTP] ↔ [AC5GaiGTP*ATP];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:isVersionOf

Gene Ontology adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway

revreaction_32

[GaiGTP] + [AC5GaolfGTP*ATP] ↔ [AC5GaolfGTPGaiGTP*ATP];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:hasPart

Gene Ontology adenylate cyclase-activating G-protein coupled receptor signaling pathway
Gene Ontology adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway

revreaction_33

[AC5Ca*ATP] + [GaiGTP] ↔ [AC5CaGaiGTP*ATP];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:isVersionOf

Gene Ontology adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway

revreaction_34

[GaiGTP] + [AC5CaGaolfGTP*ATP] ↔ [AC5CaGaolfGTPGaiGTP*ATP];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:hasPart

Gene Ontology adenylate cyclase-activating G-protein coupled receptor signaling pathway
Gene Ontology adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway

revreaction_35

[cAMP] + [PKA] ↔ [PKAcAMP2];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:hasPart

Gene Ontology protein kinase A binding
Gene Ontology cAMP binding

revreaction_36

[cAMP] + [PKAcAMP2] ↔ [PKAcAMP4];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:hasPart

Gene Ontology protein kinase A binding
Gene Ontology cAMP binding

revreaction_37

[PKAcAMP4] ↔ [PKAc] + [PKAreg];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:is

Reactome R-MMU-111925

revreaction_38

[cAMP] + [PDE4] ↔ [PDE4*cAMP];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:isVersionOf

Gene Ontology 3',5'-cyclic-AMP phosphodiesterase activity

revreaction_39

[PDE10] + 2.0 × [cAMP] ↔ [PDE10c];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:isVersionOf

Gene Ontology 3',5'-cyclic-AMP phosphodiesterase activity

revreaction_40

[cAMP] + [PDE10] ↔ [PDE10*cAMP];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:isVersionOf

Gene Ontology 3',5'-cyclic-AMP phosphodiesterase activity

revreaction_41

[cAMP] + [PDE10c] ↔ [PDE10c*cAMP];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:isVersionOf

Gene Ontology 3',5'-cyclic-AMP phosphodiesterase activity

revreaction_42

[CaM] + [Ca] ↔ [CaMCa2];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:hasPart

Gene Ontology calcium ion binding
Gene Ontology calmodulin binding

revreaction_43

[Ca] + [CaMCa2] ↔ [CaMCa4];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:isVersionOf

Gene Ontology calcium ion binding

revreaction_44

[PP2B] + [CaM] ↔ [PP2BCaM];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:hasPart

Gene Ontology protein phosphatase 2B binding
Gene Ontology calmodulin binding

revreaction_45

[PP2B] + [CaMCa4] ↔ [PP2Bc];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:hasPart	Gene Ontology protein phosphatase 2B binding
bqbiol:isVersionOf	Gene Ontology calmodulin-dependent protein phosphatase activity

revreaction_46

[PKAc] + [DARPP32] ↔ [PKAc*D32];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:hasPart

Gene Ontology protein phosphatase 1 binding
Gene Ontology protein kinase A catalytic subunit binding

revreaction_47

[PKAc] + [B56PP2A] ↔ [PKAc*B56PP2A];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:hasPart

Gene Ontology protein phosphatase 2A binding
Gene Ontology protein kinase A catalytic subunit binding

revreaction_48

[D32p34] + [PP1] ↔ [PP1D32p34];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:isVersionOf

Gene Ontology protein phosphatase 1 binding

revreaction_49

[CDK5] + [DARPP32] ↔ [CDK5*D32];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:isVersionOf	Gene Ontology phosphorylation
bqbiol:hasPart	Gene Ontology protein phosphatase 1 binding

revreaction_50

[D32p75] + [PKAc] ↔ [PKAcD32p75];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:hasPart

Gene Ontology protein phosphatase regulator activity
Gene Ontology protein kinase A catalytic subunit binding

revreaction_51

[B72PP2A] + [Ca] ↔ [B72PPA2Ca];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:hasPart

Gene Ontology protein phosphatase 2A binding
Gene Ontology calcium ion binding

revreaction_52

[B56PP2Ap] + [D32p75] ↔ [B56PP2Ap*D32p75];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:hasPart

Gene Ontology protein phosphatase 1 binding
Gene Ontology protein phosphatase 2A binding

revreaction_53

[B72PP2A] + [D32p75] ↔ [B72PP2A*D32p75];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:hasPart

Gene Ontology protein phosphatase regulator activity
Gene Ontology protein phosphatase 2A binding

revreaction_54

[D32p75] + [B72PPA2Ca] ↔ [B72PP2ACa*D32p75];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:hasPart

Gene Ontology protein phosphatase regulator activity
Gene Ontology protein phosphatase 2A binding

revreaction_55

[D32p34] + [PP2Bc] ↔ [PP2Bc*D32p34];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:hasPart

Gene Ontology protein phosphatase regulator activity
Gene Ontology protein phosphatase 2B binding

revreaction_56

[PP2BCaM] + [Ca] ↔ [PP2BCaMCa2];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:isVersionOf	Gene Ontology calmodulin-dependent protein phosphatase activity
bqbiol:hasPart	Gene Ontology calcium ion binding Gene Ontology protein phosphatase 2A binding

revreaction_57

[PP2BCaMCa2] + [Ca] ↔ [PP2Bc];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:isVersionOf	Gene Ontology calcium-dependent protein serine/threonine phosphatase activity Gene Ontology calmodulin-dependent protein phosphatase activity
bqbiol:hasPart	Gene Ontology protein phosphatase 2A binding Gene Ontology calcium ion binding

revreaction_58

[PP2B] + [CaMCa2] ↔ [PP2BCaMCa2];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:isHomologTo

Reactome R-HSA-201783

revreaction_59

[D32p75] + [B56PP2A] ↔ [B56PP2A*D32p75];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:hasPart

Gene Ontology protein phosphatase regulator activity
Gene Ontology protein phosphatase 2A binding

revreaction_60

[D32p34] + [B72PPA2Ca] ↔ [B72PP2ACa*D32p34];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:hasPart

Gene Ontology protein phosphatase regulator activity
Gene Ontology protein phosphatase 2A binding

revreaction_61

[D32p34] + [B72PP2A] ↔ [B72PP2A*D32p34];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:hasPart

Gene Ontology protein phosphatase regulator activity
Gene Ontology protein phosphatase 2A binding

irrevreaction_1

[GaolfGTP] → [GaolfGDP];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:isVersionOf

Gene Ontology GTPase activity

irrevreaction_2

[D1RDAGolf] → [Gbgolf] + [D1RDA] + [GaolfGTP];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:isVersionOf

Gene Ontology obsolete G-protein dissociation
Gene Ontology G-protein coupled receptor binding

Notes:

The second term is now obsolete, but more accurately describes this reaction.

irrevreaction_3

[GaolfGDP] + [Gbgolf] → [Golf];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:hasPart	Gene Ontology G-protein alpha-subunit binding Gene Ontology G-protein beta-subunit binding
bqbiol:isVersionOf	Gene Ontology G-protein coupled receptor binding

irrevreaction_4

[GaiGTP] → [GaiGDP];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:isVersionOf

Gene Ontology GTPase activity

irrevreaction_5

[Gbgi] + [GaiGDP] → [Gi];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:hasPart	Gene Ontology G-protein beta/gamma-subunit complex binding Gene Ontology G-protein alpha-subunit binding
bqbiol:isVersionOf	Gene Ontology G-protein coupled receptor binding

irrevreaction_6

[M4RAChGi] → [GaiGTP] + [M4RACh] + [Gbgi];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:isVersionOf

Gene Ontology obsolete G-protein dissociation
Gene Ontology G-protein coupled receptor binding

Notes:

The second term is now obsolete, but more accurately describes this reaction.

irrevreaction_7

[AC5GaolfGTP*ATP] → [cAMP] + [AC5GaolfGTP];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:is

Reactome R-MMU-170676

Notes:

This identifier may not work in the pathway browser, but works properly when entered into reactome.org search bar.

irrevreaction_8

[cAMP] + [AC5GaolfGTP] → [AC5GaolfGTP*ATP];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:isVersionOf

Reactome R-MMU-170676

Notes:

This identifier may not work in the pathway browser, but works properly when entered into reactome.org search bar.

irrevreaction_9

[AC5*ATP] → [cAMP] + [AC5];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:is

Reactome R-MMU-111930

irrevreaction_10

[cAMP] + [AC5] → [AC5*ATP];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:isVersionOf

Reactome R-MMU-111930

irrevreaction_11

[AC5GaiGTP*ATP] → [cAMP] + [AC5GaiGTP];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:is

Reactome R-MMU-170676

Notes:

This identifier may not work in the pathway browser, but works properly when entered into reactome.org search bar.

irrevreaction_12

[cAMP] + [AC5GaiGTP] → [AC5GaiGTP*ATP];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:isVersionOf

Reactome R-MMU-170676

Notes:

This identifier may not work in the pathway browser, but works properly when entered into reactome.org search bar.

irrevreaction_13

[AC5GaolfGTPGaiGTP*ATP] → [cAMP] + [AC5GaolfGTPGaiGTP];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:is

Reactome R-MMU-170676

Notes:

This identifier may not work in the pathway browser, but works properly when entered into reactome.org search bar.

irrevreaction_14

[cAMP] + [AC5GaolfGTPGaiGTP] → [AC5GaolfGTPGaiGTP*ATP];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:isVersionOf

Reactome R-MMU-170676

Notes:

This identifier may not work in the pathway browser, but works properly when entered into reactome.org search bar.

irrevreaction_15

[AC5CaGaolfGTPGaiGTP*ATP] → [cAMP] + [AC5CaGaolfGTPGaiGTP];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:is

Reactome R-MMU-170676

Notes:

This identifier may not work in the pathway browser, but works properly when entered into reactome.org search bar.

irrevreaction_16

[cAMP] + [AC5CaGaolfGTPGaiGTP] → [AC5CaGaolfGTPGaiGTP*ATP];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:isVersionOf

Reactome R-MMU-170676

Notes:

This identifier may not work in the pathway browser, but works properly when entered into reactome.org search bar.

irrevreaction_17

[AC5CaGaiGTP*ATP] → [cAMP] + [AC5CaGaiGTP];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:is

Reactome R-MMU-170676

Notes:

This identifier may not work in the pathway browser, but works properly when entered into reactome.org search bar.

irrevreaction_18

[cAMP] + [AC5CaGaiGTP] → [AC5CaGaiGTP*ATP];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:isVersionOf

Reactome R-MMU-170676

Notes:

This identifier may not work in the pathway browser, but works properly when entered into reactome.org search bar.

irrevreaction_19

[AC5Ca*ATP] → [cAMP] + [AC5Ca];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:is

Reactome R-MMU-442715

irrevreaction_20

[cAMP] + [AC5Ca] → [AC5Ca*ATP];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:isVersionOf

Reactome R-MMU-442715

irrevreaction_21

[AC5CaGaolfGTP*ATP] → [cAMP] + [AC5CaGaolfGTP];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:is

Reactome R-MMU-170676

Notes:

This identifier may not work in the pathway browser, but works properly when entered into reactome.org search bar.

irrevreaction_22

[cAMP] + [AC5CaGaolfGTP] → [AC5CaGaolfGTP*ATP];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:isVersionOf

Reactome R-MMU-170676

Notes:

This identifier may not work in the pathway browser, but works properly when entered into reactome.org search bar.

irrevreaction_23

[AC5GaolfGTP] → [AC5] + [GaolfGDP];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:isVersionOf

Gene Ontology GTPase activity

irrevreaction_24

[AC5CaGaolfGTP] → [AC5Ca] + [GaolfGDP];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:isVersionOf

Gene Ontology GTPase activity

irrevreaction_25

[AC5CaGaiGTP] → [AC5Ca] + [GaiGDP];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:isVersionOf

Gene Ontology GTPase activity

irrevreaction_26

[AC5GaiGTP] → [AC5] + [GaiGDP];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:isVersionOf

Gene Ontology GTPase activity

irrevreaction_27

[AC5GaolfGTPGaiGTP] → [AC5GaiGTP] + [GaolfGDP];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:isVersionOf

Gene Ontology GTPase activity

irrevreaction_28

[AC5GaolfGTPGaiGTP] → [AC5GaolfGTP] + [GaiGDP];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:isVersionOf

Gene Ontology GTPase activity

irrevreaction_29

[AC5CaGaolfGTPGaiGTP] → [AC5CaGaiGTP] + [GaolfGDP];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:isVersionOf

Gene Ontology GTPase activity

irrevreaction_30

[AC5CaGaolfGTPGaiGTP] → [AC5CaGaolfGTP] + [GaiGDP];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:isVersionOf

Gene Ontology GTPase activity

irrevreaction_31

[AC5GaolfGTPGaiGTP*ATP] → [GaiGDP] + [AC5GaolfGTP*ATP];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:isVersionOf

Gene Ontology GTPase activity

irrevreaction_32

[AC5GaiGTP*ATP] → [AC5*ATP] + [GaiGDP];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:isVersionOf

Gene Ontology GTPase activity

irrevreaction_33

[AC5GaolfGTPGaiGTP*ATP] → [AC5GaiGTP*ATP] + [GaolfGDP];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:isVersionOf

Gene Ontology GTPase activity

irrevreaction_34

[AC5GaolfGTP*ATP] → [AC5*ATP] + [GaolfGDP];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:isVersionOf

Gene Ontology GTPase activity

irrevreaction_35

[AC5CaGaolfGTP*ATP] → [AC5Ca*ATP] + [GaolfGDP];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:isVersionOf

Gene Ontology GTPase activity

irrevreaction_36

[AC5CaGaolfGTPGaiGTP*ATP] → [AC5CaGaolfGTP*ATP] + [GaiGDP];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:isVersionOf

Gene Ontology GTPase activity

irrevreaction_37

[AC5CaGaiGTP*ATP] → [AC5Ca*ATP] + [GaiGDP];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:isVersionOf

Gene Ontology GTPase activity

irrevreaction_38

[AC5CaGaolfGTPGaiGTP*ATP] → [AC5CaGaiGTP*ATP] + [GaolfGDP];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:isVersionOf

Gene Ontology GTPase activity

irrevreaction_39

[PDE4*cAMP] → [PDE4] + [AMP];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:isVersionOf

Gene Ontology 3',5'-cyclic-AMP phosphodiesterase activity

irrevreaction_40

[PDE10*cAMP] → [PDE10] + [AMP];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:isVersionOf

Gene Ontology 3',5'-cyclic-AMP phosphodiesterase activity

irrevreaction_41

[PDE10c*cAMP] → [PDE10c] + [AMP];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:isVersionOf

Gene Ontology 3',5'-cyclic-AMP phosphodiesterase activity

irrevreaction_42

[PKAc*D32] → [D32p34] + [PKAc];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:isVersionOf

Gene Ontology protein kinase activity

irrevreaction_43

[PKAc*B56PP2A] → [B56PP2Ap] + [PKAc];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:isVersionOf

Gene Ontology protein kinase activity

irrevreaction_44

[CDK5*D32] → [CDK5] + [D32p75];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:isVersionOf

Gene Ontology cyclin-dependent protein kinase activity

irrevreaction_45

[B56PP2Ap*D32p75] → [B56PP2Ap] + [DARPP32];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:isVersionOf

Gene Ontology protein serine/threonine phosphatase activity

irrevreaction_46

[B72PP2A*D32p75] → [B72PP2A] + [DARPP32];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:isVersionOf

Gene Ontology protein serine/threonine phosphatase activity

irrevreaction_47

[B72PP2ACa*D32p75] → [B72PPA2Ca] + [DARPP32];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:isVersionOf

Gene Ontology protein serine/threonine phosphatase activity

irrevreaction_48

[B56PP2A*D32p75] → [B56PP2A] + [DARPP32];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:isVersionOf

Gene Ontology protein serine/threonine phosphatase activity

irrevreaction_49

[B72PP2ACa*D32p34] → [B72PPA2Ca] + [DARPP32];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:isVersionOf

Gene Ontology protein serine/threonine phosphatase activity

irrevreaction_50

[B72PP2A*D32p34] → [DARPP32] + [B72PP2A];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:isVersionOf

Gene Ontology protein serine/threonine phosphatase activity

irrevreaction_51

[PP2Bc*D32p34] → [DARPP32] + [PP2Bc];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:isVersionOf

Gene Ontology calmodulin-dependent protein phosphatase activity

irrevreaction_52

[B56PP2Ap] → [B56PP2A];

Math:

(Details: $View Math$ )

Annotations:

set #1

bqbiol:isVersionOf

Gene Ontology positive regulation of protein phosphatase type 2A activity

Rules (7)

Assignment Rule (name: totalActivePKA)

totalActivePKA = mwcfcf2e7f_907a_4d25_812f_6c10a7293859-mwb320746f_6a8c_4c8b_ae55_23db454339d8

Math:

(Details: $View Math$ )

Assignment Rule (name: DApeak)

DApeak = 1/(1+exp((-ModelValue_132)*time+ModelValue_132*ModelValue_133))-1/(1+exp((-ModelValue_132)*time+ModelValue_132*(ModelValue_133+ModelValue_134)))

Math:

(Details: $View Math$ )

Assignment Rule (name: DApeak_minimum)

DApeak_minimum = ModelValue_135

Math:

(Details: $View Math$ )

Assignment Rule (name: mwbe974953_e869_4622_b4a8_745555c8d7fd)

DA = ModelValue_135+ModelValue_130*(ModelValue_137-ModelValue_136)*DApeak

Math:

(Details: $View Math$ )

Assignment Rule (name: AChdip)

AChdip = (1-1/(1+exp((-ModelValue_140)*time+ModelValue_140*ModelValue_141)))+1/(1+exp((-ModelValue_140)*time+ModelValue_140*(ModelValue_141+ModelValue_142)))

Math:

(Details: $View Math$ )

Assignment Rule (name: AChdip_maximum)

AChdip_maximum = ModelValue_143

Math:

(Details: $View Math$ )

Assignment Rule (name: mw3e1a2fbf_37b1_490c_9528_6cb6bbf11b21)

ACh = (1-ModelValue_138)*ModelValue_143+ModelValue_138*(ModelValue_144+(ModelValue_145-ModelValue_144)*AChdip)

Math:

(Details: $View Math$ )

Spine

Spatial dimensions: 3.0 Compartment size: 1.0E-15

GaiGTP

Compartment: Spine

Initial concentration: 2.3562470443292

GaolfGDP

Compartment: Spine

Initial concentration: 0.00514744794169027

Gbgolf

Compartment: Spine

Initial concentration: 107.875380092904

GaolfGTP

Compartment: Spine

Initial concentration: 1.13940415390363

D1RDAGolf

Compartment: Spine

Initial concentration: 3.70188602073145

Golf

Compartment: Spine

Initial concentration: 1102.52804493589

D1RGolf

Compartment: Spine

Initial concentration: 785.894688950477

D1RDA

Compartment: Spine

Initial concentration: 16.100094198358

D1R

Compartment: Spine

Initial concentration: 1194.30333083043

cAMP

Compartment: Spine

Initial concentration: 91.6467576551524

Compartment: Spine

Initial concentration: 60.0

Constant

AC5

Compartment: Spine

Initial concentration: 0.507493613791483

AC5GaolfGTP

Compartment: Spine

Initial concentration: 0.397626017086897

CaM

Compartment: Spine

Initial concentration: 7686.15789228991

CaMCa2

Compartment: Spine

Initial concentration: 316.776054644554

CaMCa4

Compartment: Spine

Initial concentration: 2.47080976475754

PDE4

Compartment: Spine

Initial concentration: 1531.9927671361

PKA

Compartment: Spine

Initial concentration: 1100.85005741739

PKAcAMP2

Compartment: Spine

Initial concentration: 26.2312279909643

PKAcAMP4

Compartment: Spine

Initial concentration: 0.831786420159049

PKAreg

Compartment: Spine

Initial concentration: 72.0869281714876

PKAc

Compartment: Spine

Initial concentration: 11.5386581348021

PP2B

Compartment: Spine

Initial concentration: 5.40475669921873

PP2Bc

Compartment: Spine

Initial concentration: 194.502520839594

PP2BCaM

Compartment: Spine

Initial concentration: 1380.87227011886

PP2BCaMCa2

Compartment: Spine

Initial concentration: 419.196440881025

DARPP32

Compartment: Spine

Initial concentration: 37271.6543135964

PKAc*D32

Compartment: Spine

Initial concentration: 7.16774795405187

D32p34

Compartment: Spine

Initial concentration: 0.678978545756906

B72PP2A

Compartment: Spine

Initial concentration: 860.232017549719

PKAc*B56PP2A

Compartment: Spine

Initial concentration: 16.40971542072

B56PP2Ap

Compartment: Spine

Initial concentration: 410.242885172213

CDK5

Compartment: Spine

Initial concentration: 233.496415726183

PP1

Compartment: Spine

Initial concentration: 1493.10639547125

CDK5*D32

Compartment: Spine

Initial concentration: 1566.50358427382

D32p75

Compartment: Spine

Initial concentration: 8659.68104422894

PKAcD32p75

Compartment: Spine

Initial concentration: 36.9708066619157

B72PPA2Ca

Compartment: Spine

Initial concentration: 51.6139210529853

B56PP2Ap*D32p75

Compartment: Spine

Initial concentration: 296.047711354635

B72PP2A*D32p75

Compartment: Spine

Initial concentration: 805.333502271791

B72PP2ACa*D32p75

Compartment: Spine

Initial concentration: 44.6960093760864

PP1D32p34

Compartment: Spine

Initial concentration: 506.893604528755

PP2Bc*D32p34

Compartment: Spine

Initial concentration: 0.0240114612997978

B72PP2A*D32p34

Compartment: Spine

Initial concentration: 224.645801649792

Compartment: Spine

Initial concentration: 10.0

AMP

Compartment: Spine

Initial concentration: 0.0

Constant

AC5Ca

Compartment: Spine

Initial concentration: 0.0338357229453947

AC5CaGaolfGTP

Compartment: Spine

Initial concentration: 0.0265277448296902

AC5GaiGTP

Compartment: Spine

Initial concentration: 1.70785338199615

AC5CaGaiGTP

Compartment: Spine

Initial concentration: 0.113888299015711

B56PP2A

Compartment: Spine

Initial concentration: 711.07555205532

B56PP2A*D32p75

Compartment: Spine

Initial concentration: 566.224135997113

B72PP2ACa*D32p34

Compartment: Spine

Initial concentration: 13.4787480996268

PDE4*cAMP

Compartment: Spine

Initial concentration: 468.007232863897

AC5GaolfGTPGaiGTP

Compartment: Spine

Initial concentration: 4.39135728748305E-4

AC5CaGaolfGTPGaiGTP

Compartment: Spine

Initial concentration: 2.92811632030252E-5

M4R

Compartment: Spine

Initial concentration: 1529.69994816436

M4RACh

Compartment: Spine

Initial concentration: 25.650119219421

M4RGi

Compartment: Spine

Initial concentration: 214.722656407666

Compartment: Spine

Initial concentration: 1095.19571044122

M4RAChGi

Compartment: Spine

Initial concentration: 229.927276208549

Gbgi

Compartment: Spine

Initial concentration: 460.154356942568

GaiGDP

Compartment: Spine

Initial concentration: 0.299804540897635

ACh

Compartment: Spine

Initial concentration: 100.0

PDE10c

Compartment: Spine

Initial concentration: 0.230445425050315

PDE10

Compartment: Spine

Initial concentration: 246.931440841991

PDE10*cAMP

Compartment: Spine

Initial concentration: 452.609318325671

PDE10c*cAMP

Compartment: Spine

Initial concentration: 0.228795407287519

ATP

Compartment: Spine

Initial concentration: 5000000.0

Constant

AC5GaolfGTPGaiGTP*ATP

Compartment: Spine

Initial concentration: 0.109825804214832

AC5GaiGTP*ATP

Compartment: Spine

Initial concentration: 427.086542949603

AC5GaolfGTP*ATP

Compartment: Spine

Initial concentration: 99.5522607546951

AC5*ATP

Compartment: Spine

Initial concentration: 126.887958343277

AC5CaGaolfGTP*ATP

Compartment: Spine

Initial concentration: 6.63679803850652

AC5CaGaiGTP*ATP

Compartment: Spine

Initial concentration: 28.4724047907866

AC5CaGaolfGTPGaiGTP*ATP

Compartment: Spine

Initial concentration: 0.00732171483303589

AC5Ca*ATP

Compartment: Spine

Initial concentration: 8.459194407526

PP1*AKAR3p

Compartment: Spine

Initial concentration: 0.0

PKAc*AKAR3

Compartment: Spine

Initial concentration: 0.0

totalActivePKA

Compartment: Spine

Initial concentration: 35.1161215095719

BioModels Database

BIOMD0000000635 - Nair2015 - Interaction between neuromodulators via GPCRs - Effect on cAMP/PKA signaling (D1 Neuron)

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