1. Information
    majorVersion:3 minorVersion:0 projectID:local projectVersionID:undef fileName:/home/ikeda/eclipse/workspace/macrophage/csml/ok/csml/17669557.csml convertedTime:2009.07.01.11:06

  2. Original Literature
  3. Model OverView
  4. Model Abstracts
  5. Model Detail
  6. Download
Original Literature Model OverView
Publication
Title Multifunctional effects of bradykinin on glial cells in relation to potentialanti-inflammatory effects.
Authors Noda M, Sasaki K, Ifuku M, Wada K.
Affiliation Laboratory of Pathophysiology, Graduate School of Pharmaceutical Sciences,Kyushu University, Fukuoka 812-8582, Japan. noda@phar.kyushu-u.ac.jp
Abstract Kinins have been reported to be produced and act at the site of injury andinflammation. Despite many reports that they are likely to initiate a particularcascade of inflammatory events, bradykinin (BK) has anti-inflammatory effects inthe brain mediated by glial cells. In the present review, we have attempted todescribe the complex responses and immediate reaction of glial cells to BK.Glial cells express BK receptors and induce Ca(2+)-dependent signal cascades.Among them, production of prostaglandin E(2) (PGE(2)), via B(1) receptors inprimary cultured microglia, has a negative feedback effect on lipopolysaccharide(LPS)-induced release of tumor necrosis factor-alpha (TNF-alpha) via increasingintracellular cyclic adenosine monophosphate (cAMP). In addition, BKup-regulates the production of neurotrophic factors such as nerve growth factor(NGF) via B(2) receptors in astrocytes. These results suggest that BK may haveanti-inflammatory and neuroprotective effects in the brain through multiplefunctions on glial cells. These observations may help to understand the paradoxon the role of kinins in the central nervous system and may be useful fortherapeutic strategy.
PMID 17669557
Model Abstract

Entity

G010262:IL-6 G010279:MMP-9 G010329:TNF-alpha G010389:IL-1beta G010514:iNOS G011021:BDKRB1 G012199:BDNF G029941:COX2 MO000000289:TNF-alpha MO000007384:IL-6 MO000009818:NGF MO000016597:IL-1beta MO000016882:LPS MO000019394:TLR4 MO000021201:iNOS MO000021939:PGE2 e1: e10: e11:Bradykinin:Bradykinin receptor e12:PLA2 e13:LPS:TLR4 e14:calcium e15:ATP e16:P2Y e17:ATP:P2Y e18:P2X e19:ATP:P2X e2: e20:BAPTA-AM e21:NS398 e22:RpcAMP e23:NGF e24:endotheline-1 e25:ETR e26:ET:ETR e3: e4: e5:Bradykinin e50: e51: e52: e53: e54: e55: e56: e57: e58: e59: e6:Bradykinin receptor 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 p26 p27 p28 p29 p3 p30 p4 p5 p6 p7 p8 p9
Model Detail
772.0, 1038.0
36.0, 36.0

IL-6

--

G010262

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p5

p6

true true true true

csml-variable:Double

m93248

10

false

infinite

0

unit false false false
TRANSFACG010262

--

Go back
625.0, 983.0
34.0, 34.0

MMP-9

--

G010279

cso30:c:mRNA

cso30:i:CC_CellComponent

--

p1

--

true true true true

csml-variable:Double

m93262

10

false

infinite

0

unit false false false
TRANSFACG010279

--

Go back
503.0, 909.0
38.0, 38.0

TNF-alpha

--

G010329

cso30:c:mRNA

cso30:i:CC_CellComponent

--

p8

p9

true true true true

csml-variable:Double

m93309

10

false

infinite

0

unit false false false
TRANSFACG010329

--

Go back
461.0, 1123.0
34.0, 34.0

IL-1beta

--

G010389

cso30:c:mRNA

cso30:i:CC_CellComponent

--

p10

p11

true true true true

csml-variable:Double

m93364

10

false

infinite

0

unit false false false
TRANSFACG010389

--

Go back
379.0, 1013.0
30.0, 30.0

iNOS

--

G010514

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p17

p18

true true true true

csml-variable:Double

m93479

10

false

infinite

0

unit false false false
TRANSFACG010514

--

Go back
732.0, 1130.0
36.0, 36.0

BDKRB1

--

G011021

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p19 p20

--

true true true true

csml-variable:Double

m93907

10

false

infinite

0

unit false false false
TRANSFACG011021

--

Go back
520.0, 1114.0
36.0, 36.0

BDNF

--

G012199

cso30:c:mRNA

cso30:i:CC_CellComponent

--

p26

--

true true true true

csml-variable:Double

m94997

10

false

infinite

0

unit false false false
TRANSFACG012199

--

Go back
544.0, 978.0
36.0, 36.0

COX2

--

G029941

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p4

--

true true true true

csml-variable:Double

m108639

10

false

infinite

0

unit false false false
TRANSFACG029941

--

Go back
110.0, 908.0
48.0, 48.0

TNF-alpha

--

MO000000289

cso30:c:Protein

cso30:i:CC_CellComponent

--

p9

--

true true true true

csml-variable:Double

m230

10

false

infinite

0

unit false false false
InterProIPR003636
TRANSPATHMO000000289

--

Go back
1113.0, 1039.0
34.0, 34.0

IL-6

--

MO000007384

cso30:c:Protein

cso30:i:CC_CellComponent

--

p6

--

true true true true

csml-variable:Double

m871

10

false

infinite

0

unit false false false
InterProIPR003573
TRANSPATHMO000007384

--

Go back
1094.0, 1132.0
40.0, 40.0

NGF

--

MO000009818

cso30:c:Protein

cso30:i:CC_CellComponent

--

p27

--

true true true true

csml-variable:Double

m1169

10

false

infinite

0

unit false false false
InterProIPR002072
TRANSPATHMO000009818

--

Go back
111.0, 1129.0
38.0, 38.0

IL-1beta

--

MO000016597

cso30:c:Protein

cso30:i:CC_CellComponent

--

p11

--

true true true true

csml-variable:Double

m1591

10

false

infinite

0

unit false false false
TRANSPATHMO000016597

--

Go back
1205.0, 575.0
34.0, 34.0

LPS

--

MO000016882

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p7

true true true true

csml-variable:Double

m155666

10

false

infinite

0

unit false false false
TRANSPATHMO000016882

--

Go back
1005.0, 571.0
42.0, 42.0

TLR4

--

MO000019394

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p7

true true true true

csml-variable:Double

m3961

10

false

infinite

0

unit false false false
InterProIPR000157
TRANSPATHMO000019394

--

Go back
273.0, 771.0
34.0, 34.0

iNOS

--

MO000021201

cso30:c:Protein

cso30:i:CC_CellComponent

--

p18 p30

--

true true true true

csml-variable:Double

m5576

10

false

infinite

0

unit false false false
TRANSPATHMO000021201

--

Go back
91.0, 525.0
29.0, 29.0

PGE2

--

MO000021939

cso30:c:Protein

cso30:i:CC_CellComponent

--

p21 p22

--

true true true true

csml-variable:Double

m346644

10

false

infinite

0

unit false false false
TRANSPATHMO000021939

--

Go back
184.75, 98.99690800911759
856.2594311764528, 1243.2886940682085

--

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
193.0, 118.0
829.9775981223105, 1167.545103664102

--

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
998.5, 442.0
31.0, 60.0

Bradykinin:Bradykinin receptor

--

e11

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p2

p1 p3 p4 p5 p6 p8 p9 p10 p11 p12 p17 p18 p19 p21 p23 p26 p27

true true true true

csml-variable:Double

m11

0

false

infinite

0

unit false false false

--

Go back
699.0, 985.1557093425605
54.083044982698965, 28.844290657439448

PLA2

--

e12

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p3

--

true true true true

csml-variable:Double

m12

0

false

infinite

0

unit false false false

--

Go back
1014.5, 666.0
31.0, 60.0

LPS:TLR4

--

e13

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p7

p8 p9 p10 p11 p20 p22

true true true true

csml-variable:Double

m13

0

false

infinite

0

unit false false false

--

Go back
725.5, 455.0980087558255
33.33695805677165, 33.90199124417456

calcium

--

e14

cso30:c:SmallMolecule

cso30:i:CC_Cytosol

--

p12 p14 p15

p28 p29 p30

true true true true

csml-variable:Double

m14

0

false

infinite

0

unit false false false

--

Go back
1160.0, 208.19865642994242
44.18426103646833, 24.301343570057583

ATP

--

e15

cso30:c:SmallMolecule

cso30:i:CC_Extracellular

--

--

p13 p16

true true true true

csml-variable:Double

m15

0

false

infinite

0

unit false false false

--

Go back
986.5, 154.0
39.0, 60.0

P2Y

--

e16

cso30:c:Protein

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

--

p13

true true true true

csml-variable:Double

m16

0

false

infinite

0

unit false false false

--

Go back
990.5, 242.0
31.0, 60.0

ATP:P2Y

--

e17

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p13

p14

true true true true

csml-variable:Double

m17

0

false

infinite

0

unit false false false

--

Go back
902.5, 98.0
39.0, 60.0

P2X

--

e18

cso30:c:Protein

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

--

p16

true true true true

csml-variable:Double

m18

0

false

infinite

0

unit false false false

--

Go back
798.5, 94.0
31.0, 60.0

ATP:P2X

--

e19

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p16

p15

true true true true

csml-variable:Double

m19

0

false

infinite

0

unit false false false

--

Go back
184.75, 98.99690800911759
856.2594311764528, 1243.2886940682085

--

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
97.0, 749.390243902439
50.48780487804878, 28.60975609756097

BAPTA-AM

--

e20

cso30:c:SmallMolecule

cso30:i:CC_Extracellular

--

--

p18

true true true true

csml-variable:Double

m20

0

false

infinite

0

unit false false false

--

Go back
100.0, 1019.0
60.0, 34.0

NS398

--

e21

cso30:c:SmallMolecule

cso30:i:CC_Extracellular

--

--

p9

true true true true

csml-variable:Double

m21

0

false

infinite

0

unit false false false

--

Go back
60.0, 831.0
60.0, 34.0

RpcAMP

--

e22

cso30:c:SmallMolecule

cso30:i:CC_Extracellular

--

--

p9

true true true true

csml-variable:Double

m22

0

false

infinite

0

unit false false false

--

Go back
580.0, 1136.0
60.0, 32.0

NGF

--

e23

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p23 p24

p27

true true true true

csml-variable:Double

m23

0

false

infinite

0

unit false false false

--

Go back
431.0, 1439.46
54.72, 41.04

endotheline-1

--

e24

cso30:c:Protein

cso30:i:CC_Extracellular

--

--

p25

true true true true

csml-variable:Double

m24

0

false

infinite

0

unit false false false

--

Go back
398.5, 1286.0
39.0, 60.0

ETR

--

e25

cso30:c:Protein

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

--

p25

true true true true

csml-variable:Double

m25

0

false

infinite

0

unit false false false

--

Go back
498.5, 1286.0
31.0, 60.0

ET:ETR

--

e26

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p25

p24

true true true true

csml-variable:Double

m26

0

false

infinite

0

unit false false false

--

Go back
201.87518862352903, 116.12209663264667
822.0090539293948, 1209.0383168211513

--

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
233.5567875770579, 146.09117672382234
758.6458560223374, 1149.1001566387988

--

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
1239.0, 333.18717047451673
45.09666080843586, 29.312829525483302

Bradykinin

--

e5

cso30:c:Protein

cso30:i:CC_Extracellular

--

--

p2

true true true true

csml-variable:Double

m5

0

false

infinite

0

unit false false false

--

Go back
351.194539690755, 785.5041728666623
525.1040876206854, 476.2117144716461

--

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
407.90969254364074, 796.7896981967015
307.0441033759688, 461.5440025269342

--

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
358.0394719316205, 791.8601813760374
511.4142231389546, 463.4996974528957

--

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
359.0173193946012, 792.8380288390182
509.4585282129927, 461.5440025269342

--

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
351.194539690755, 785.5041728666623
525.1040876206854, 476.2117144716461

--

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
351.194539690755, 785.5041728666623
525.1040876206854, 476.2117144716461

--

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
359.0173193946012, 792.8380288390182
509.4585282129927, 461.5440025269342

--

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
734.5107451792252, 981.0736654628205
32.80561820799179, 29.697717535655766

--

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
648.4601684369159, 1117.9723102801315
92.89550898317525, 84.09488181634822

--

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
351.194539690755, 785.5041728666623
525.1040876206854, 476.2117144716461

--

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
982.5, 338.0
39.0, 60.0

Bradykinin receptor

--

e6

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p2

true true true true

csml-variable:Double

m6

0

false

infinite

0

unit false false false

--

Go back
474.95861858561614, 997.1287238080713
16.629274895537936, 8.00668791266642

--

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
474.40332002633477, 973.2508857589747
56.91810232633477, 102.45258418740256

--

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
498.2811580754317, 1039.8867128727322
8.884776948501024, 8.884776948501028

--

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
196.0, 104.0
839.7237354966342, 1189.8668429177399

--

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
199.0, 125.0
805.5569854171277, 1169.6687428256696

--

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
207.0, 146.0
801.8791759029863, 1154.3288303559784

--

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
629.0, 899.0
25.0, 25.0

p1

p1

cso30:i:ME_GeneExpression

cso30:i:CC_Cytosol

--

e11

G010279

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c5 : 1
stoichiometry:c1 : 1

m11*0.1

nodelay

--

true

0

false

PMID: 17669557, 15240011, 15991247, 16935468, 10501190 In astrocytes, BK induced expression of matrix metalloproteinase-9, phospholipase A2 and COX-2 and increased expression and secretion of IL-6

Go back
467.0, 1069.0
21.0, 21.0

p10

p10

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e13 e11

G010389

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c26 : 1
stoichiometry:c31 : 1
stoichiometry:c25 : 1

m13*0.1

nodelay

--

true

0

false

PMID: 17669557, 17402969 BK receptors in microglia mediate anti-inflammatory or neuroprotective effects, namely the inhibition of LPS-induced release of TNF-¦Á and IL-1¦Â.

Go back
283.0, 1137.0
21.0, 21.0

p11

p11

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

G010389 e13 e11

MO000016597

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c28 : 1
stoichiometry:c29 : 1
stoichiometry:c30 : 1
stoichiometry:c27 : 1

m93364*m13*0.1

nodelay

--

true

0

false

PMID: 17669557, 17402969 BK receptors in microglia mediate anti-inflammatory or neuroprotective effects, namely the inhibition of LPS-induced release of TNF-¦Á and IL-1¦Â.

Go back
816.0, 458.0
27.0, 27.0

p12

p12

cso30:i:ME_ChangeInMaterialConcentration

cso30:i:CC_Cytosol

--

e11

e14

true true true true

--

and

mass

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

m11*0.1

nodelay

--

true

0

false

PMID: 17669557 BK-induced Ca2+ rises in primary cultured microglia were observed.

Go back
1087.0, 209.0
21.0, 21.0

p13

p13

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

e16 e15

e17

true true true true

--

and

mass

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

m16*m15*0.1

nodelay

--

true

0

false

PMID: 17669557 ATP binds to receptor P2X and P2Y.

Go back
820.0, 394.0
27.0, 27.0

p14

p14

cso30:i:ME_ChangeInMaterialConcentration

cso30:i:CC_Cytosol

--

e17

e14

true true true true

--

and

mass

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

m17*0.1

nodelay

--

true

0

false

PMID: 17669557 ATP evoked an increase of [Ca2+] even in cells which did not respond to BK, suggesting that the majority of cultured microglial cells possess ATP receptors while only a minority have functional BK receptors.

Go back
729.0, 383.0
25.0, 25.0

p15

p15

cso30:i:ME_ChangeInMaterialConcentration

cso30:i:CC_Cytosol

--

e19

e14

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c43 : 1
stoichiometry:c39 : 1

m19*0.1

nodelay

--

true

0

false

PMID: 17669557 ATP evoked an increase of [Ca2+] even in cells which did not respond to BK, suggesting that the majority of cultured microglial cells possess ATP receptors while only a minority have functional BK receptors.

Go back
1085.0, 39.0
25.0, 25.0

p16

p16

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

e18 e15

e19

true true true true

--

and

mass

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

m18*m15*0.1

nodelay

--

true

0

false

PMID: 17669557 ATP binds to receptor P2X and P2Y.

Go back
386.0, 964.0
23.0, 23.0

p17

p17

cso30:i:ME_GeneExpression

cso30:i:CC_Cytosol

--

e11

G010514

true true true true

--

and

mass

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

m11*0.1

nodelay

--

true

0

false

PMID: 17669557 The immunocytochemical analysis using a specific antibody against iNOS showed stronger expression of iNOS in BK-treated microglia identified by isolectin B4-labeling.

Go back
279.0, 1021.0
21.0, 21.0

p18

p18

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

G010514 e11 e20

MO000021201

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c46 : 1
stoichiometry:c48 : 1
stoichiometry:c49 : 1
stoichiometry:c47 : 1

m93479*m11*0.1

nodelay

--

true

0

false

PMID: 17669557 The immunocytochemical analysis using a specific antibody against iNOS showed stronger expression of iNOS in BK-treated microglia identified by isolectin B4-labeling. PMID: 17669557 This increase was prevented by the treatment of the cells with 10 ¦ÌM BAPTA-AM, a membrane-permeable Ca2+ chelator, hinting to a link between BK induced Ca2+ signaling and iNOS expression.

Go back
686.0, 1080.0
23.0, 23.0

p19

p19

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e11

G011021

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c53 : 1
stoichiometry:c52 : 1

m11*0.1

nodelay

--

true

0

false

PMID: 17669557, 12551746, 15145558 In microglia, the inducible expression of B1 was shown by application of LPS and BK.

Go back
1130.0, 356.0
23.0, 23.0

p2

p2

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

e6 e5

e11

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c2 : 1
stoichiometry:c3 : 1
stoichiometry:c4 : 1

m6*m5*0.1

nodelay

--

true

0

false

PMID: 17669557 Bradykinin binds to receptor BDKRB1.

Go back
784.0, 1098.0
27.0, 27.0

p20

p20

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e13

G011021

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c55 : 1
stoichiometry:c54 : 1

m13*0.1

nodelay

--

true

0

false

PMID: 17669557, 12551746, 15145558 In microglia, the inducible expression of B1 was shown by application of LPS and BK.

Go back
725.0, 527.0
25.0, 25.0

p21

p21

cso30:i:ME_UnknownProduction

cso30:i:CC_Cytosol

--

e11

MO000021939

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c57 : 1
stoichiometry:c56 : 1

m11*0.1

nodelay

--

true

0

false

PMID: 17669557 PGE2 release was also increased in astrocytes after application of LPS or BK.

Go back
698.0, 584.0
23.0, 23.0

p22

p22

cso30:i:ME_UnknownProduction

cso30:i:CC_Cytosol

--

e13

MO000021939

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c59 : 1
stoichiometry:c58 : 1

m13*0.1

nodelay

--

true

0

false

PMID: 17669557 PGE2 release was also increased in astrocytes after application of LPS or BK.

Go back
599.0, 1077.5
21.5, 21.5

p23

p23

cso30:i:ME_GeneExpression

cso30:i:CC_Cytosol

--

e11

e23

true true true true

--

and

mass

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

m11*0.1

nodelay

--

true

0

false

PMID: 17669557 BK also up-regulated mRNA for neurotrophic factors such as nerve growth factor (NGF).

Go back
596.0, 1202.0
27.0, 27.0

p24

p24

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e26

e23

true true true true

--

and

mass

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

m26*0.1

nodelay

--

true

0

false

PMID: 17669557 BK and ET, but not substance P (SubP) at concentration of 100 nM increased the mRNA level for NGF.

Go back
447.0, 1377.0
21.0, 21.0

p25

p25

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

e25 e24

e26

true true true true

--

and

mass

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

m25*m24*0.1

nodelay

--

true

0

false

PMID: 17669557 Endothelin-1 binds to its receptor.

Go back
544.0, 1058.0
27.0, 27.0

p26

p26

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e11

G012199

true true true true

--

and

mass

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

m11*0.1

nodelay

--

true

0

false

PMID: 17669557 We also observed up-regulation of brain-derived neurotrophic factor (BDNF) mRNA level.

Go back
858.0, 1140.0
23.0, 23.0

p27

p27

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

e23 e11

MO000009818

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c69 : 1
stoichiometry:c71 : 1
stoichiometry:c70 : 1

m23*m11*0.1

nodelay

--

true

0

false

PMID: 17669557 The amount of NGF was significantly increased by 100 nM BK after 6 h, but not after 3 h of incubation in accordance with the time course of up-regulation of NGF mRNA level.

Go back
201.0, 373.0
30.0, 30.0

p28

p28

cso30:i:ME_IonTransportThroughIonChannel

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

e14

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c73 : 1

m14*0.1

nodelay

--

true

0

false

--

Go back
125.0, 309.0
30.0, 30.0

p29

p29

cso30:i:CE_CellMigration

cso30:i:CC_Extracellular

--

e14

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c72 : 1

m14*0.1

nodelay

--

true

0

false

--

Go back
714.0, 923.5
24.5, 24.5

p3

p3

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e11

e12

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c7 : 1
stoichiometry:c6 : 1

m11*0.1

nodelay

--

true

0

false

PMID: 17669557, 15240011, 15991247, 16935468, 10501190 In astrocytes, BK induced expression of matrix metalloproteinase-9, phospholipase A2 and COX-2 and increased expression and secretion of IL-6

Go back
333.0, 657.0
30.0, 30.0

p30

p30

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

e14

MO000021201

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c74 : 1
stoichiometry:c75 : 1

m14*0.1

nodelay

--

true

0

false

--

Go back
548.0, 898.0
27.0, 27.0

p4

p4

cso30:i:ME_GeneExpression

cso30:i:CC_Cytosol

--

e11

G029941

true true true true

--

and

mass

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

m11*0.1

nodelay

--

true

0

false

PMID: 17669557, 15240011, 15991247, 16935468, 10501190 In astrocytes, BK induced expression of matrix metalloproteinase-9, phospholipase A2 and COX-2 and increased expression and secretion of IL-6

Go back
776.0, 954.0
27.0, 27.0

p5

p5

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e11

G010262

true true true true

--

and

mass

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

m11*0.1

nodelay

--

true

0

false

PMID: 17669557, 15240011, 15991247, 16935468, 10501190 In astrocytes, BK induced expression of matrix metalloproteinase-9, phospholipase A2 and COX-2 and increased expression and secretion of IL-6.

Go back
894.0, 1044.0
23.0, 23.0

p6

p6

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

G010262 e11

MO000007384

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c12 : 1
stoichiometry:c14 : 1
stoichiometry:c13 : 1

m93248*m11*0.1

nodelay

--

true

0

false

PMID: 17669557, 15240011, 15991247, 16935468, 10501190 In astrocytes, BK induced expression of matrix metalloproteinase-9, phospholipase A2 and COX-2 and increased expression and secretion of IL-6.

Go back
1111.0, 582.0
21.0, 21.0

p7

p7

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

MO000019394 MO000016882

e13

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c15 : 1
stoichiometry:c16 : 1
stoichiometry:c17 : 1

m3961*m155666*0.1

nodelay

--

true

0

false

PMID: 17669557 LPS binds TLR4.

Go back
509.0, 867.0
25.0, 25.0

p8

p8

cso30:i:ME_GeneExpression

cso30:i:CC_Cytosol

--

e13 e11

G010329

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c19 : 1
stoichiometry:c23 : 1
stoichiometry:c18 : 1

m13*0.1

nodelay

--

true

0

false

PMID: 17669557, 17402969 BK receptors in microglia mediate anti-inflammatory or neuroprotective effects, namely the inhibition of LPS-induced release of TNF-¦Á and IL-1¦Â.

Go back
304.0, 918.0
27.0, 27.0

p9

p9

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

G010329 e13 e11 e21 e22

MO000000289

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c20 : 1
stoichiometry:c22 : 1
stoichiometry:c24 : 1
stoichiometry:c50 : 1
stoichiometry:c51 : 1
stoichiometry:c21 : 1

m93309*m13*0.1

nodelay

--

true

0

false

PMID: 17669557, 17402969 BK receptors in microglia mediate anti-inflammatory or neuroprotective effects, namely the inhibition of LPS-induced release of TNF-¦Á and IL-1¦Â. PMID: 17669557 BK-induced attenuation of LPS-induced TNF-¦Á formation was suppressed by 10 ¦ÌM NS398, a cyclooxygenase-2 (COX-2) inhibitor, and 50 ¦ÌM RpcAMP, a membrane-permeable cAMP inhibitor.

Go back
642.0, 924.0

c1

c1

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
799.2909647409962, 502.0

c10

c10

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
790.0, 981.0

c11

c11

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
808.0, 1056.0

c12

c12

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
917.0, 1056.0

c13

c13

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
909.4515160270151, 502.0

c14

c14

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
1047.0, 592.0

c15

c15

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1139.9992494957532, 592.0

c16

c16

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1051.290361057329, 603.0

c17

c17

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
523.0, 892.0

c18

c18

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
541.5229033622026, 702.0

c19

c19

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
1022.0, 368.0

c2

c2

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
338.9978375455748, 928.0

c20

c20

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
166.0, 932.0

c21

c21

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
338.5927899798607, 701.0

c22

c22

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
537.0810160942233, 485.0

c23

c23

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
334.3381619090647, 482.0

c24

c24

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
478.0, 1090.0

c25

c25

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
494.57079745800485, 707.0

c26

c26

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
157.0, 1148.0

c27

c27

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
311.99206019471603, 1141.0

c28

c28

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
310.8198448425326, 706.0

c29

c29

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
1160.896058159444, 352.0

c3

c3

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
306.9172323681713, 487.0

c30

c30

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
490.6468291574682, 490.0

c31

c31

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
767.0, 472.0

c32

c32

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
851.0, 472.0

c33

c33

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
1026.0, 192.0

c34

c34

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1116.0, 220.0

c35

c35

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1028.9525178510432, 226.0

c36

c36

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
765.5891820405523, 418.0

c37

c37

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
853.272366595694, 284.0

c38

c38

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
742.0, 408.0

c39

c39

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1036.2165110278465, 378.0

c4

c4

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
942.0, 61.18229987249658

c40

c40

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1107.5777087639997, 71.15541752799933

c41

c41

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
814.079026979346, 52.0

c42

c42

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
747.0592000467291, 154.0

c43

c43

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
395.6135719910779, 987.0

c44

c44

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
415.1953995193477, 485.0

c45

c45

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
307.9942379249057, 1029.0

c46

c46

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
290.0, 813.0

c47

c47

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
306.3308775182616, 484.0

c48

c48

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
131.0, 778.0

c49

c49

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
658.1668684837998, 490.0

c5

c5

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
160.0, 941.9239343855849

c50

c50

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
120.0, 859.0

c51

c51

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
708.0, 1103.0

c52

c52

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
707.6367608342204, 502.0

c53

c53

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
774.4, 1122.0

c54

c54

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
809.9025708613195, 724.0

c55

c55

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
128.0, 540.0

c56

c56

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
757.7702313307393, 476.0

c57

c57

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
127.96531352707285, 541.7441642395535

c58

c58

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
728.6349150843756, 601.3891571012332

c59

c59

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
726.0, 948.0

c6

c6

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
610.0, 1099.0

c60

c60

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
621.3897535373395, 496.0

c61

c61

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
610.0, 1176.0

c62

c62

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
435.0, 1346.0

c63

c63

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
458.0, 1406.0

c64

c64

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
467.0, 1342.3065262678806

c65

c65

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
530.0, 1234.777599141211

c66

c66

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
546.6079254665552, 1085.0

c67

c67

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
573.8395246113791, 492.0

c68

c68

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
640.0, 1152.0

c69

c69

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
738.2185066227685, 497.0

c7

c7

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
881.0, 1152.0

c70

c70

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
874.6561203454374, 502.0

c71

c71

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
162.76986492274577, 329.90504569034044

c72

c72

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
238.9000224029751, 391.26081165623236

c73

c73

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
370.13565207714316, 480.0

c74

c74

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
301.5777087639997, 687.0

c75

c75

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
562.0, 925.0

c8

c8

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
580.7374620736007, 487.0

c9

c9

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back