1. Information
    majorVersion:3 minorVersion:0 projectID:local projectVersionID:undef fileName:/home/ikeda/eclipse/workspace/macrophage/csml/ok/csml/11890659.csml convertedTime:2009.07.01.10:40

  2. Original Literature
  3. Model OverView
  4. Model Abstracts
  5. Model Detail
  6. Download
Original Literature Model OverView
Publication
Title The atrial natriuretic peptide regulates the production of inflammatorymediators in macrophages.
Authors Kiemer AK, Vollmar AM.
Affiliation Department of Pharmacy, Centre of Drug Research, University of Munich, Germany.Alexandra.Kiemer@cup.uni-muenchen.de
Abstract The atrial natriuretic peptide (ANP), a member of the natriuretic peptidefamily, is a cardiovascular hormone which possesses well defined natriuretic,diuretic, and vasodilating properties. Most of the biological effects of ANParemediated through its guanylyl cyclase coupled A receptor. Because ANP and itsreceptors have been shown to be expressed and differentially regulated in theimmune system, it has been suggested that ANP has an immunomodulatory potency.Much investigation of the effects of ANP on the activation of macrophages hasbeen carried out. ANP was shown to inhibit the lipopolysaccharide (LPS)-inducedexpression of inducible nitric oxide synthase (iNOS) in macrophages in anautocrine fashion. ANP in this context was shown to reduce significantly theactivation of NF-kappaB and to destabilise iNOS mRNA. ANP, furthermore, cansignificantly reduce the LPS-induced secretion of tumour necrosis factor alpha(TNFalpha) in macrophages. The relevance of these findings on a regulatory rolefor ANP on TNFalpha in humans was shown by the fact that ANP significantlyreduces the release of TNFalpha in whole human blood. It was furthermore shownto attenuate the release of interleukin 1beta (IL1beta). Interestingly, ANP didnot affect the secretion of the anti-inflammatory cytokines IL10 and IL1receptor antagonist (IL1ra). In summary, ANP was shown to reduce the secretionof inflammatory mediators in macrophages. Therefore, this cardiovascular hormonemay possess anti-inflammatory potential.
PMID 11890659
Model Abstract

Entity

e1: e10: e11:BNP:NPR-A e12:ANP e13:ANP:NPR-A e14:NPR-B e15:CNP e16:CNP:NPR-B e17:NPR-C e18:BNP:NPR-C e19:ANP:NPR-C e2: e20:CNP:NPR-C e21:CNP:NPR-C e22:ANP:NPR-C e23:BNP:NPR-C e24:Nitric oxide e25:L-Arginine e26:eNOS e27:nNOS e28:iNOS e29:LPS e3: e30:TLR e31:LPS:TLR e32:iNOS{active} e33:NF-kappaB e34:NF-kappaB{active} e35:iNOS e36:TNF-alpha e37:AP1 e38:AP1{active} e39:p38 e4: e40:p38{active} e41:IFN-gamma e42:Iterferon-gamma receptor e43:IFN-gamma:IFN-gamma receptor e5:BNP e50: e51: e52: e53: e54: e55: e56: e57: e58: e59: e6:NPR-A e60: e61: e62: e7: e8: e9:

Process

p1 p10 p11 p12 p13 p14 p15 p16 p17 p18 p19 p2 p20 p21 p22 p23 p24 p25 p3 p4 p5 p6 p7 p8 p9
Model Detail
102.49533904994783, 155.18176147041893
869.514092126505, 1324.1038406069072

--

e1

cso30:c:EntityBiologicalCompartment

cso30:i:CC_PlasmaMembrane

--

--

--

true true true true

csml-variable:Double

m1

0

false

infinite

0

unit false true false

--

Go back
110.87304678530987, 175.42007555513894
842.8254235110891, 1243.4368326674528

--

e10

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cytosol

--

--

--

true true true true

csml-variable:Double

m10

0

false

infinite

0

unit false true false

--

Go back
936.5, 366.0
31.0, 60.0

BNP:NPR-A

--

e11

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p1

--

true true true true

csml-variable:Double

m11

0

false

infinite

0

unit false false false

--

Go back
1152.0, 368.5878734622145
47.55711775043937, 30.912126537785586

ANP

--

e12

cso30:c:Protein

cso30:i:CC_Extracellular

--

--

p2 p5

true true true true

csml-variable:Double

m12

0

false

infinite

0

unit false false false

--

Go back
932.5, 446.0
31.0, 60.0

ANP:NPR-A

--

e13

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p2

p18 p21 p23 p25

true true true true

csml-variable:Double

m13

0

false

infinite

0

unit false false false

--

Go back
934.5, 580.7996485061511
35.23022847100176, 54.200351493848856

NPR-B

--

e14

cso30:c:Protein

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

--

p3

true true true true

csml-variable:Double

m14

0

false

infinite

0

unit false false false

--

Go back
1122.0, 593.347100175747
44.8506151142355, 29.152899824253083

CNP

--

e15

cso30:c:Protein

cso30:i:CC_Extracellular

--

--

p3 p6

true true true true

csml-variable:Double

m15

0

false

infinite

0

unit false false false

--

Go back
932.5, 666.0
31.0, 60.0

CNP:NPR-B

--

e16

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p3

--

true true true true

csml-variable:Double

m16

0

false

infinite

0

unit false false false

--

Go back
784.5, 142.0
39.0, 60.0

NPR-C

--

e17

cso30:c:Protein

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p8 p10 p12

p4 p5 p6

true true true true

csml-variable:Double

m17

0

false

infinite

0

unit false false false

--

Go back
660.5, 134.0
31.0, 60.0

BNP:NPR-C

--

e18

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p4

p11

true true true true

csml-variable:Double

m18

0

false

infinite

0

unit false false false

--

Go back
516.5, 134.0
31.0, 60.0

ANP:NPR-C

--

e19

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p5

p9

true true true true

csml-variable:Double

m19

0

false

infinite

0

unit false false false

--

Go back
102.49533904994783, 155.18176147041893
869.514092126505, 1324.1038406069072

--

e2

cso30:c:EntityBiologicalCompartment

cso30:i:CC_PlasmaMembrane_ExternalSideOfPlasmaMembrane_

--

--

--

true true true true

csml-variable:Double

m2

0

false

infinite

0

unit false true false

--

Go back
392.5, 134.0
31.0, 60.0

CNP:NPR-C

--

e20

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p6

p7

true true true true

csml-variable:Double

m20

0

false

infinite

0

unit false false false

--

Go back
296.5, 230.0
31.0, 60.0

CNP:NPR-C

--

e21

cso30:c:Complex

cso30:i:CC_Cytosol

--

p7

p8

true true true true

csml-variable:Double

m21

0

false

infinite

0

unit false false false

--

Go back
522.5, 294.49791712343784
26.092742819557113, 50.50208287656216

ANP:NPR-C

--

e22

cso30:c:Complex

cso30:i:CC_Cytosol

--

p9

p10

true true true true

csml-variable:Double

m22

0

false

infinite

0

unit false false false

--

Go back
684.5, 278.0
31.0, 60.0

BNP:NPR-C

--

e23

cso30:c:Complex

cso30:i:CC_Cytosol

--

p11

p12

true true true true

csml-variable:Double

m23

0

false

infinite

0

unit false false false

--

Go back
445.0, 568.1470588235295
53.088235294117645, 31.852941176470587

Nitric oxide

--

e24

cso30:c:SmallMolecule

cso30:i:CC_Cytosol

--

p13 p14 p15

--

true true true true

csml-variable:Double

m24

0

false

infinite

0

unit false false false

--

Go back
256.0, 568.1017661900758
56.291000841042894, 31.89823380992431

L-Arginine

--

e25

cso30:c:SmallMolecule

cso30:i:CC_Cytosol

--

--

p13 p14 p15

true true true true

csml-variable:Double

m25

0

false

infinite

0

unit false false false

--

Go back
343.0, 496.6877641376534
49.9657878848863, 30.81223586234655

eNOS

--

e26

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p13

true true true true

csml-variable:Double

m26

0

false

infinite

0

unit false false false

--

Go back
209.0, 618.3683839806802
45.618836788086135, 28.131616019319782

nNOS

--

e27

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p14

true true true true

csml-variable:Double

m27

0

false

infinite

0

unit false false false

--

Go back
229.0, 666.4199999999998
37.44, 28.080000000000002

iNOS

--

e28

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p17

true true true true

csml-variable:Double

m28

0

false

infinite

0

unit false false false

--

Go back
28.0, 740.8166526492851
55.029436501261564, 31.183347350714886

LPS

--

e29

cso30:c:SmallMolecule

cso30:i:CC_Extracellular

--

--

p16

true true true true

csml-variable:Double

m29

0

false

infinite

0

unit false false false

--

Go back
119.8856208924779, 173.42010638235985
834.7335284414448, 1287.6271507830263

--

e3

cso30:c:EntityBiologicalCompartment

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

--

--

true true true true

csml-variable:Double

m3

0

false

infinite

0

unit false true false

--

Go back
143.5, 619.1933216168717
32.374340949033396, 49.80667838312829

TLR

--

e30

cso30:c:Protein

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

--

p16

true true true true

csml-variable:Double

m30

0

false

infinite

0

unit false false false

--

Go back
128.5, 826.0
31.0, 60.0

LPS:TLR

--

e31

cso30:c:Complex

cso30:i:CC_Cytosol

--

p16

p17 p21 p25

true true true true

csml-variable:Double

m31

0

false

infinite

0

unit false false false

--

Go back
348.0, 721.1
39.2, 29.4

iNOS{active}

--

e32

cso30:c:Protein

cso30:i:CC_Cytosol

--

p17

p15

true true true true

csml-variable:Double

m32

0

false

infinite

0

unit false false false

--

Go back
569.0, 589.5098611390622
45.38941436908835, 27.990138860937815

NF-kappaB

--

e33

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p18 p25

true true true true

csml-variable:Double

m33

0

false

infinite

0

unit false false false

--

Go back
638.0, 725.9268464479775
44.71322197625277, 27.57315355202254

NF-kappaB{active}

--

e34

cso30:c:Protein

cso30:i:CC_Cytosol

--

p18 p25

p19 p20

true true true true

csml-variable:Double

m34

0

false

infinite

0

unit false false false

--

Go back
480.0, 1041.2698961937717
55.7439446366782, 29.730103806228374

iNOS

--

e35

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p19

--

true true true true

csml-variable:Double

m35

0

false

infinite

0

unit false false false

--

Go back
607.0, 1042.0380622837372
50.55363321799308, 26.961937716262977

TNF-alpha

--

e36

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p20 p22

--

true true true true

csml-variable:Double

m36

0

false

infinite

0

unit false false false

--

Go back
784.0, 885.02
40.64, 30.48

AP1

--

e37

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p21

true true true true

csml-variable:Double

m37

0

false

infinite

0

unit false false false

--

Go back
805.0, 1038.82
46.239999999999995, 34.68

AP1{active}

--

e38

cso30:c:Protein

cso30:i:CC_Cytosol

--

p21

p22

true true true true

csml-variable:Double

m38

0

false

infinite

0

unit false false false

--

Go back
597.0, 519.243217960711
21.56127221702526, 49.756782039289064

p38

--

e39

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p23

true true true true

csml-variable:Double

m39

0

false

infinite

0

unit false false false

--

Go back
152.05764230115872, 205.3372099782562
770.3894856240836, 1223.7929435912324

--

e4

cso30:c:EntityBiologicalCompartment

cso30:i:CC_PlasmaMembrane_InternalSideOfPlasmaMembrane_

--

--

--

true true true true

csml-variable:Double

m4

0

false

infinite

0

unit false true false

--

Go back
830.0, 577.1262862488308
19.445275958840035, 44.87371375116932

p38{active}

--

e40

cso30:c:Protein

cso30:i:CC_Cytosol

--

p23

p18

true true true true

csml-variable:Double

m40

0

false

infinite

0

unit false false false

--

Go back
26.0, 286.3523725834799
43.30404217926186, 28.14762741652021

IFN-gamma

--

e41

cso30:c:Protein

cso30:i:CC_Extracellular

--

--

p24

true true true true

csml-variable:Double

m41

0

false

infinite

0

unit false false false

--

Go back
119.5, 265.87346221441123
33.882249560632694, 52.12653778558875

Iterferon-gamma receptor

--

e42

cso30:c:Protein

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

--

p24

true true true true

csml-variable:Double

m42

0

false

infinite

0

unit false false false

--

Go back
128.5, 362.0
31.0, 60.0

IFN-gamma:IFN-gamma receptor

--

e43

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p24

p23

true true true true

csml-variable:Double

m43

0

false

infinite

0

unit false false false

--

Go back
1094.0, 149.46133567662565
44.67486818980669, 29.038664323374338

BNP

--

e5

cso30:c:Protein

cso30:i:CC_Extracellular

--

--

p1 p4

true true true true

csml-variable:Double

m5

0

false

infinite

0

unit false false false

--

Go back
286.551039296538, 918.790851106418
472.85820625190127, 449.7429972598096

--

e50

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearEnvelopeLumen

--

--

--

true true true true

csml-variable:Double

m50

0

false

infinite

0

unit false true false

--

Go back
337.6232477930189, 929.4491063179989
276.4943701361212, 435.89054354544174

--

e51

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearPore

--

--

--

true true true true

csml-variable:Double

m51

0

false

infinite

0

unit false true false

--

Go back
292.71492652887196, 924.7935810493108
460.53043178723374, 437.737537374024

--

e52

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearInnerMembrane

--

--

--

true true true true

csml-variable:Double

m52

0

false

infinite

0

unit false true false

--

Go back
293.59548184777674, 925.7170779636019
458.76932114942383, 435.89054354544174

--

e53

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearLumen

--

--

--

true true true true

csml-variable:Double

m53

0

false

infinite

0

unit false true false

--

Go back
286.551039296538, 918.790851106418
472.85820625190127, 449.7429972598096

--

e54

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearOuterMembrane

--

--

--

true true true true

csml-variable:Double

m54

0

false

infinite

0

unit false true false

--

Go back
286.551039296538, 918.790851106418
472.85820625190127, 449.7429972598096

--

e55

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Nucleus

--

--

--

true true true true

csml-variable:Double

m55

0

false

infinite

0

unit false true false

--

Go back
293.59548184777674, 925.7170779636019
458.76932114942383, 435.89054354544174

--

e56

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Nucleoplasm

--

--

--

true true true true

csml-variable:Double

m56

0

false

infinite

0

unit false true false

--

Go back
631.7287243072367, 1103.490233964656
29.54158260527818, 28.047064132136697

--

e57

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearBody

--

--

--

true true true true

csml-variable:Double

m57

0

false

infinite

0

unit false true false

--

Go back
554.2398562436106, 1232.7798019654226
83.65275529596018, 79.4207346290424

--

e58

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Nucleolus

--

--

--

true true true true

csml-variable:Double

m58

0

false

infinite

0

unit false true false

--

Go back
286.551039296538, 918.790851106418
472.85820625190127, 449.7429972598096

--

e59

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearEnvelope

--

--

--

true true true true

csml-variable:Double

m59

0

false

infinite

0

unit false true false

--

Go back
928.1063268892794, 249.0
40.39367311072055, 62.14411247803164

NPR-A

--

e6

cso30:c:Protein

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

--

p1 p2

true true true true

csml-variable:Double

m6

0

false

infinite

0

unit false false false

--

Go back
398.00105792011703, 1118.6529228316972
14.974724599847281, 7.561661568871143

--

e60

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Chromatin

--

--

--

true true true true

csml-variable:Double

m60

0

false

infinite

0

unit false true false

--

Go back
397.5010094785484, 1096.1022586503263
51.25496526078195, 96.75808235960329

--

e61

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearChromosome

--

--

--

true true true true

csml-variable:Double

m61

0

false

infinite

0

unit false true false

--

Go back
419.00309246599886, 1159.0343447378737
8.000775065097661, 8.39094481167291

--

e62

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearCentromere

--

--

--

true true true true

csml-variable:Double

m62

0

false

infinite

0

unit false true false

--

Go back
113.91948596180515, 160.51005999966915
852.7224284166372, 1267.209509774373

--

e7

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cell

--

--

--

true true true true

csml-variable:Double

m7

0

false

infinite

0

unit false true false

--

Go back
116.96592513830043, 182.87508333287383
818.0267864247267, 1245.6985107341084

--

e8

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cell_WithoutCellWall_

--

--

--

true true true true

csml-variable:Double

m8

0

false

infinite

0

unit false true false

--

Go back
125.08976294228788, 205.2401066660785
814.2920454288707, 1229.361486909634

--

e9

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cytoplasm

--

--

--

true true true true

csml-variable:Double

m9

0

false

infinite

0

unit false true false

--

Go back
1020.0, 268.0
23.0, 23.0

p1

p1

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

e6 e5

e11

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c1 : 1
stoichiometry:c2 : 1
stoichiometry:c3 : 1

m6*m5*0.1

nodelay

--

true

0

false

PMID: 11890659 The guanylyl cyclases NPR-A and NPR-B contain an extracellular, ligand binding domain whereby NPR-A binds ANP and BNP.

Go back
524.0, 380.0
24.0, 24.0

p10

p10

cso30:i:ME_UnknownDegradation

cso30:i:CC_Cytosol

--

e22

e17

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c25 : 1
stoichiometry:c26 : 1

m22*0.1

nodelay

--

true

0

false

PMID: 11890659 NPR-C has the potency to internalise and clear the natriuretic peptides

Go back
665.0, 232.0
23.0, 23.0

p11

p11

cso30:i:ME_Internalization

cso30:i:CC_Cytosol

--

e18

e23

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c27 : 1
stoichiometry:c28 : 1

m18*0.1

nodelay

--

true

0

false

PMID: 11890659 NPR-C has the potency to internalise and clear the natriuretic peptides.

Go back
689.0, 372.0
23.0, 23.0

p12

p12

cso30:i:ME_UnknownDegradation

cso30:i:CC_Cytosol

--

e23

e17

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c29 : 1
stoichiometry:c30 : 1

m23*0.1

nodelay

--

true

0

false

PMID: 11890659 NPR-C has the potency to internalise and clear the natriuretic peptides

Go back
361.0, 572.5
22.5, 22.5

p13

p13

cso30:i:ME_Oxidation

cso30:i:CC_Cytosol

--

e25 e26

e24

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c31 : 1
stoichiometry:c33 : 1
stoichiometry:c32 : 1

m25*m26*0.1

nodelay

--

true

0

false

PMID: 11890659, 8532063, 10865843 In the organism nitric oxide is synthesised by nitric oxide synthases (NOS) from the amino acid L-arginine. Two constitutive nitric oxide synthases, the endothelial NOS (eNOS, NOS I) and the neuronal NOS (nNOS; NOS III), produce NO that mainly serves as vasodilator.

Go back
357.0, 625.0
21.0, 21.0

p14

p14

cso30:i:ME_Oxidation

cso30:i:CC_Cytosol

--

e25 e27

e24

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c34 : 1
stoichiometry:c36 : 1
stoichiometry:c35 : 1

m25*m27*0.1

nodelay

--

true

0

false

PMID: 11890659, 8532063, 10865843 In the organism nitric oxide is synthesised by nitric oxide synthases (NOS) from the amino acid L-arginine. Two constitutive nitric oxide synthases, the endothelial NOS (eNOS, NOS I) and the neuronal NOS (nNOS; NOS III), produce NO that mainly serves as vasodilator.

Go back
361.0, 669.0
21.0, 21.0

p15

p15

cso30:i:ME_Oxidation

cso30:i:CC_Cytosol

--

e25 e32

e24

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c37 : 1
stoichiometry:c39 : 1
stoichiometry:c38 : 1

m25*m32*0.1

nodelay

--

true

0

false

PMID: 11890659, 8532063, 9303203 NO produced by the inducible isoform of the enzyme (iNOS) is an important mediator of host defence.

Go back
85.0, 701.0
21.0, 21.0

p16

p16

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

e29 e30

e31

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c40 : 1
stoichiometry:c41 : 1
stoichiometry:c42 : 1

m29*m30*0.1

nodelay

--

true

0

false

PMID: 11890659, 8532063, 1429562 Induction occurs after exposure of cells to cytokines and bacterial products, such as lipopolysaccharides (LPS).

Go back
252.0, 724.0
23.0, 23.0

p17

p17

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

e28 e31

e32

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c43 : 1
stoichiometry:c45 : 1
stoichiometry:c44 : 1

m28*m31*0.1

nodelay

--

true

0

false

PMID: 11890659, 8532063, 1429562 Induction occurs after exposure of cells to cytokines and bacterial products, such as lipopolysaccharides (LPS).

Go back
649.0, 653.0
21.0, 21.0

p18

p18

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

e33 e40 e13

e34

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c46 : 1
stoichiometry:c48 : 1
stoichiometry:c70 : 1
stoichiometry:c47 : 1

m33*m40*0.1

nodelay

--

true

0

false

PMID: 11890659, 9593677, 11257311 ANP was shown to inhibit markedly the activation of the transcription factor NF-kappaB. The LPS-induced expression of TNF-alpha is inhibited by ANP through binding to the NPR-A. The inhibitory action involves transcriptional processes with a reduced activation of NF-kappaB and AP1.

Go back
496.0, 940.0
23.0, 23.0

p19

p19

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e34

e35

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c50 : 1
stoichiometry:c49 : 1

m34*0.1

nodelay

--

true

0

false

PMID: 11890659, 7508926 ANP was shown to inhibit markedly the activation of the transcription factor NF-kappaB which is crucial for the induction of iNOS in murine macrophages.

Go back
1032.0, 372.0
23.0, 23.0

p2

p2

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

e6 e12

e13

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c4 : 1
stoichiometry:c5 : 1
stoichiometry:c6 : 1

m6*m12*0.1

nodelay

--

true

0

false

PMID: 11890659 The guanylyl cyclases NPR-A and NPR-B contain an extracellular, ligand binding domain whereby NPR-A binds ANP and BNP.

Go back
620.0, 912.0
23.0, 23.0

p20

p20

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e34

e36

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c52 : 1
stoichiometry:c51 : 1

m34*0.1

nodelay

--

true

0

false

PMID: 11890659, 1429562 TNF-alpha is a central proinflammatory cytokine and is regulated transcriptionally; the two transcription factors NF-kappaB and AP1 are involved.

Go back
817.0, 968.0
23.0, 23.0

p21

p21

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

e37 e13 e31

e38

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c53 : 1
stoichiometry:c57 : 1
stoichiometry:c59 : 1
stoichiometry:c54 : 1

m37*m31*0.1

nodelay

--

true

0

false

PMID: 11890659, 10861050 Besides the reduced activation of NF-kappaB, ANP markedly inhibited AP1 activity in LPS activated macrophages.

Go back
700.0, 1044.0
23.0, 23.0

p22

p22

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e38

e36

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c56 : 1
stoichiometry:c55 : 1

m38*0.1

nodelay

--

true

0

false

PMID: 11890659, 1429562 TNF-alpha is a central proinflammatory cytokine and is regulated transcriptionally; the two transcription factors NF-kappaB and AP1 are involved.

Go back
739.0, 531.0
25.0, 25.0

p23

p23

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

e39 e13 e43

e40

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c60 : 1
stoichiometry:c62 : 1
stoichiometry:c66 : 1
stoichiometry:c61 : 1

m39*m43*0.1

nodelay

--

true

0

false

PMID: 11890659, 11257311 The inhibitory action of ANP on the interferon-gamma mediated activation of the p38 mitogen activated protein kinase was suggested to be the upstream step responsible for the attenuated activation of NF-kappaB in macrophages.

Go back
70.0, 338.0
19.0, 19.0

p24

p24

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

e41 e42

e43

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c63 : 1
stoichiometry:c64 : 1
stoichiometry:c65 : 1

m41*m42*0.1

nodelay

--

true

0

false

PMID: 11890659, 11257311 The inhibitory action of ANP on the interferon-gamma mediated activation of the p38 mitogen activated protein kinase was suggested to be the upstream step responsible for the attenuated activation of NF-kappaB in macrophages.

Go back
573.0, 665.0
21.0, 21.0

p25

p25

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

e33 e31 e13

e34

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c67 : 1
stoichiometry:c58 : 1
stoichiometry:c69 : 1
stoichiometry:c68 : 1

m33*m31*0.1

nodelay

--

true

0

false

PMID: 11890659, 7508926 ANP was shown to inhibit markedly the activation of the transcription factor NF-kappaB, which is crucial for the induction of iNOS in murine macrophages.

Go back
1038.0, 598.0
19.0, 19.0

p3

p3

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

e14 e15

e16

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c7 : 1
stoichiometry:c8 : 1
stoichiometry:c9 : 1

m14*m15*0.1

nodelay

--

true

0

false

PMID: 11890659 NPR-B binds CNP.

Go back
727.0, 60.0
25.0, 25.0

p4

p4

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

e17 e5

e18

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c10 : 1
stoichiometry:c11 : 1
stoichiometry:c12 : 1

m17*m5*0.1

nodelay

--

true

0

false

PMID: 11890659 NPR-C has the potency to internalise and clear the natriuretic peptides.

Go back
759.0, 3.0
25.0, 25.0

p5

p5

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

e17 e12

e19

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c14 : 1
stoichiometry:c13 : 1
stoichiometry:c15 : 1

m17*m12*0.1

nodelay

--

true

0

false

PMID: 11890659 NPR-C has the potency to internalise and clear the natriuretic peptides.Moreover, an increasing number of reports show that several biological effects of ANP are mediated through this ¡Èclearance¡É receptor (NPR-C).

Go back
499.0, 19.0
26.0, 26.0

p6

p6

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

e17 e15

e20

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c16 : 1
stoichiometry:c17 : 1
stoichiometry:c18 : 1

m17*m15*0.1

nodelay

--

true

0

false

PMID: 11890659 NPR-C has the potency to internalise and clear the natriuretic peptides.

Go back
394.0, 247.5
25.5, 25.5

p7

p7

cso30:i:ME_Internalization

cso30:i:CC_Cytosol

--

e20

e21

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c19 : 1
stoichiometry:c20 : 1

m20*0.1

nodelay

--

true

0

false

PMID: 11890659 NPR-C has the potency to internalise and clear the natriuretic peptides.

Go back
300.0, 331.5
24.5, 24.5

p8

p8

cso30:i:ME_UnknownDegradation

cso30:i:CC_Cytosol

--

e21

e17

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c21 : 1
stoichiometry:c22 : 1

m21*0.1

nodelay

--

true

0

false

PMID: 11890659 NPR-C has the potency to internalise and clear the natriuretic peptides

Go back
523.0, 231.0
25.0, 25.0

p9

p9

cso30:i:ME_Internalization

cso30:i:CC_Cytosol

--

e19

e22

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c23 : 1
stoichiometry:c24 : 1

m19*0.1

nodelay

--

true

0

false

PMID: 11890659 NPR-C has the potency to internalise and clear the natriuretic peptides.

Go back
969.0, 280.0

c1

c1

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
752.3557680678887, 91.71023729377444

c10

c10

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
759.7743274289251, 77.88675197836484

c11

c11

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
696.5954059927715, 85.0

c12

c12

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
789.9109542525209, 32.39079027829912

c13

c13

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
775.6480838483988, 35.82839827989399

c14

c14

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
554.8110489392186, 24.0

c15

c15

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
532.2100193962015, 41.46635547894302

c16

c16

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
530.9155238698951, 49.38577546363582

c17

c17

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
428.9509778128281, 45.0

c18

c18

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
407.14812275204815, 194.0

c19

c19

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1045.7183125418119, 179.0

c2

c2

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
336.0, 260.0

c20

c20

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
312.0, 290.0

c21

c21

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
325.0, 181.64280339782485

c22

c22

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
533.0, 194.0

c23

c23

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
536.0, 256.0

c24

c24

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
536.0, 345.0

c25

c25

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
548.0, 193.06732457713366

c26

c26

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
676.0, 194.0

c27

c27

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
681.0, 255.0

c28

c28

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
701.0, 338.0

c29

c29

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
972.5288579520637, 291.0

c3

c3

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
707.0, 209.20555715377026

c30

c30

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
312.0, 584.0

c31

c31

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
384.0, 584.0

c32

c32

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
369.0, 528.0

c33

c33

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
310.0, 600.0

c34

c34

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
378.0, 601.5347985803924

c35

c35

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
255.0, 633.0

c36

c36

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
299.0, 600.0

c37

c37

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
382.0, 605.5369606578714

c38

c38

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
369.0, 697.9834024717477

c39

c39

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
969.0, 302.0

c4

c4

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
70.0, 727.9619305082008

c40

c40

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
111.50999569531754, 662.0

c41

c41

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
99.0, 722.0

c42

c42

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
252.0, 694.0

c43

c43

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
275.0, 736.0

c44

c44

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
160.0, 752.6870234923429

c45

c45

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
607.0, 618.0

c46

c46

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
660.0, 674.0

c47

c47

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
677.5508668509282, 604.0

c48

c48

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
508.0, 963.0

c49

c49

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1063.0, 384.0

c5

c5

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
521.6532144897373, 754.0

c50

c50

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
632.0, 935.0

c51

c51

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
635.2014087267618, 754.0

c52

c52

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
809.0, 916.0

c53

c53

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
828.1666305094546, 991.0

c54

c54

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
666.0, 1056.0

c55

c55

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
731.0, 1056.0

c56

c56

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
832.9185055807897, 506.0

c57

c57

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
160.0, 684.0297608173178

c58

c58

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
160.0, 859.0

c59

c59

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
969.7811348571815, 395.0

c6

c6

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
619.0, 544.0

c60

c60

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
764.0, 552.0

c61

c61

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
767.7764773813565, 481.0

c62

c62

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
58.0, 315.0

c63

c63

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
94.74881713413272, 309.0

c64

c64

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
89.0, 354.0

c65

c65

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
160.0, 396.0

c66

c66

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
585.8462884367482, 618.0

c67

c67

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
594.0, 684.0

c68

c68

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
597.5068274895857, 484.0

c69

c69

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
970.0, 608.0

c7

c7

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
673.3534831144775, 486.0

c70

c70

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
1065.0, 608.0

c8

c8

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
970.0105394839528, 617.0

c9

c9

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back