KEGG   PATHWAY: cfa04270
Entry
cfa04270                    Pathway                                
Name
Vascular smooth muscle contraction - Canis lupus familiaris (dog)
Description
The vascular smooth muscle cell (VSMC) is a highly specialized cell whose principal function is contraction. On contraction, VSMCs shorten, thereby decreasing the diameter of a blood vessel to regulate the blood flow and pressure.
The principal mechanisms that regulate the contractile state of VSMCs are changes in cytosolic Ca2+ concentration ([Ca2+]c). In response to vasoconstrictor stimuli, Ca2+ is mobilized from intracellular stores and/or the extracellular space to increase [Ca2+]c in VSMCs. The increase in [Ca2+]c, in turn, activates the Ca2+-CaM-MLCK pathway and stimulates MLC20 phosphorylation, leading to myosin-actin interactions and, hence, the development of contractile force. The sensitivity of contractile myofilaments or MLC20 phosphorylation to Ca2+ can be secondarily modulated by other signaling pathways. During receptor stimulation, the contractile force is greatly enhanced by the inhibition of myosin phosphatase. Rho/Rho kinase, PKC, and arachidonic acid have been proposed to play a pivotal role in this enhancement.
The signaling events that mediate relaxation include the removal of a contractile agonist (passive relaxation) and activation of cyclic nucleotide-dependent signaling pathways in the continued presence of a contractile agonist (active relaxation). Active relaxation occurs through the inhibition of both Ca2+ mobilization and myofilament Ca2+ sensitivity in VSMCs.
Class
Organismal Systems; Circulatory system
Pathway map
cfa04270  Vascular smooth muscle contraction
cfa04270

Other DBs
GO: 0014829
Organism
Canis lupus familiaris (dog) [GN:cfa]
Gene
403866  ADRA1A; alpha-1A adrenergic receptor [KO:K04135]
403962  ADRA1B; alpha-1B adrenergic receptor [KO:K04136]
111092035  ADRA1D; alpha-1D adrenergic receptor [KO:K04137]
403783  AGT; angiotensinogen [KO:K09821]
403836  AGTR1; type-1 angiotensin II receptor [KO:K04166]
403424  EDN1; endothelin-1 precursor [KO:K16366]
403508  EDN2; endothelin-2 precursor [KO:K16367]
403406  EDN3; endothelin-3 precursor [KO:K05227]
450187  EDNRA; endothelin-1 receptor precursor [KO:K04197]
403579  AVP; vasopressin-neurophysin 2-copeptin precursor [KO:K05242]
481142  AVPR1A; vasopressin V1a receptor [KO:K04226]
488578  AVPR1B; vasopressin V1b receptor [KO:K04227]
403928  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
403914  GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
478207  PLA2G5; phospholipase A2 group V isoform X5 [KO:K01047] [EC:3.1.1.4]
489045  PLA2G12B; group XIIB secretory phospholipase A2-like protein isoform X2 [KO:K01047] [EC:3.1.1.4]
478514  PLA2G12A; group XIIA secretory phospholipase A2 [KO:K01047] [EC:3.1.1.4]
487398  PLA2G2D; group IID secretory phospholipase A2 [KO:K01047] [EC:3.1.1.4]
487397  PLA2G2F; group IIF secretory phospholipase A2 isoform X1 [KO:K01047] [EC:3.1.1.4]
404011  PLA2G1B; phospholipase A2 preproprotein [KO:K01047] [EC:3.1.1.4]
489997  PLA2G10; group 10 secretory phospholipase A2 [KO:K01047] [EC:3.1.1.4]
486361  PLA2G3; group 3 secretory phospholipase A2 [KO:K01047] [EC:3.1.1.4]
487399  PLA2G2E; group IIE secretory phospholipase A2 [KO:K01047] [EC:3.1.1.4]
102151235  PLA2G2C; putative inactive group IIC secretory phospholipase A2 isoform X1 [KO:K01047] [EC:3.1.1.4]
487514  PLA2G4E; cytosolic phospholipase A2 epsilon isoform X1 [KO:K16342] [EC:3.1.1.4]
480048  PLA2G4A; cytosolic phospholipase A2 isoform X1 [KO:K16342] [EC:3.1.1.4]
487512  PLA2G4B; cytosolic phospholipase A2 beta [KO:K16342] [EC:3.1.1.4]
487515  PLA2G4F; cytosolic phospholipase A2 zeta isoform X1 [KO:K16342] [EC:3.1.1.4]
608811  PLA2G4D; cytosolic phospholipase A2 delta isoform X1 [KO:K16342] [EC:3.1.1.4]
481256  PLA2G6; 85/88 kDa calcium-independent phospholipase A2 isoform X2 [KO:K16343] [EC:3.1.1.4]
475366  CYP4A38; cytochrome P450 4A38 [KO:K07425] [EC:1.14.14.80]
610385  CYP4A11; cytochrome P450, family 4, subfamily A, polypeptide 11 [KO:K07425] [EC:1.14.14.80]
403984  KCNMA1; calcium-activated potassium channel subunit alpha-1 [KO:K04936]
482856  KCNU1; potassium channel subfamily U member 1 isoform X1 [KO:K05274]
403983  KCNMB1; calcium-activated potassium channel subunit beta-1 [KO:K04937]
488179  KCNMB2; calcium-activated potassium channel subunit beta-2 isoform X1 [KO:K04938]
488085  KCNMB3; calcium-activated potassium channel subunit beta-3 isoform X1 [KO:K04939]
403516  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X17 [KO:K04850]
484724  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X15 [KO:K04851]
480915  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853]
490244  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S isoform X2 [KO:K04857]
474584  CALM2; calmodulin-2 [KO:K02183]
607269  CALML6; calmodulin-like protein 6 isoform X1 [KO:K02183]
487146  CALML5; calmodulin-like protein 5 [KO:K02183]
480416  CALM1; calmodulin-1 [KO:K02183]
476428  CALM3; calmodulin-3 isoform X2 [KO:K02183]
478351  CALML4; calmodulin-like protein 4 isoform X2 [KO:K02183]
102153034  calmodulin-like protein 3 [KO:K02183]
488012  MYLK; myosin light chain kinase, smooth muscle isoform X1 [KO:K00907] [EC:2.7.11.18]
475345  MYLK3; myosin light chain kinase 3 [KO:K00907] [EC:2.7.11.18]
488190  myosin light chain kinase family member 4 isoform X18 [KO:K00907] [EC:2.7.11.18]
477187  MYLK2; myosin light chain kinase 2, skeletal/cardiac muscle [KO:K00907] [EC:2.7.11.18]
606992  MYL6B; myosin light chain 6B [KO:K12751]
607030  MYL6; myosin light polypeptide 6 isoform X1 [KO:K12751]
485856  MYL9; myosin regulatory light polypeptide 9 [KO:K12755]
479497  MYH10; myosin-10 isoform X6 [KO:K10352]
479836  MYH11; myosin-11 isoform X1 [KO:K10352]
481280  MYH9; myosin-9 [KO:K10352]
100688336  MYH14; myosin-14 isoform X3 [KO:K10352]
477160  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
485773  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
476034  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X2 [KO:K05858] [EC:3.1.4.11]
100856190  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
476548  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
486628  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X2 [KO:K04959]
481746  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
490904  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
489968  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
100855828  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
494005  PRKCD; protein kinase C delta type [KO:K06068] [EC:2.7.11.13]
609934  PRKCE; protein kinase C epsilon type isoform X3 [KO:K18050] [EC:2.7.11.13]
490722  PRKCH; protein kinase C eta type [KO:K18051] [EC:2.7.11.13]
478013  PRKCQ; protein kinase C theta type isoform X1 [KO:K18052] [EC:2.7.11.13]
491857  ARAF; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
475526  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
484648  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
478347  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
611939  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
477575  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
100855877  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
608135  CALD1; caldesmon isoform X4 [KO:K12327]
477587  ACTA2; actin, aortic smooth muscle isoform X1 [KO:K12313]
475792  ACTG2; actin, gamma-enteric smooth muscle [KO:K12315]
403557  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
403558  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
403609  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
475411  PPP1R12A; protein phosphatase 1 regulatory subunit 12A isoform X2 [KO:K06270]
490230  PPP1R12B; protein phosphatase 1 regulatory subunit 12B isoform X12 [KO:K12329]
100683226  PPP1R12C; protein phosphatase 1 regulatory subunit 12C isoform X1 [KO:K17457]
102154318  GNA12; guanine nucleotide-binding protein subunit alpha-12 isoform X3 [KO:K04346]
490901  GNA13; guanine nucleotide-binding protein subunit alpha-13 isoform X1 [KO:K04639]
479409  ARHGEF12; rho guanine nucleotide exchange factor 12 isoform X1 [KO:K07532]
100856354  ARHGEF1; rho guanine nucleotide exchange factor 1 isoform X4 [KO:K12330]
490402  ARHGEF11; rho guanine nucleotide exchange factor 11 isoform X1 [KO:K12331]
403954  RHOA; transforming protein RhoA [KO:K04513]
480181  ROCK1; rho-associated protein kinase 1 isoform X1 [KO:K04514] [EC:2.7.11.1]
482970  ROCK2; rho-associated protein kinase 2 isoform X1 [KO:K17388] [EC:2.7.11.1]
403960  ADORA2A; adenosine receptor A2a [KO:K04266]
403410  ADORA2B; adenosine receptor A2b [KO:K04267]
484429  PTGIR; prostacyclin receptor [KO:K04263]
403946  CALCA; calcitonin isoform 1 preproprotein [KO:K12332]
100187714  CRSP-3; calcitonin receptor-stimulating peptide 3 precursor [KO:K12332]
100187715  CRSP-4; calcitonin receptor-stimulating peptide 4 precursor [KO:K12332]
403414  CRSP-2; calcitonin receptor-stimulating peptide 2 precursor [KO:K12332]
403415  CALCB; calcitonin receptor-stimulating peptide 1 precursor [KO:K12332]
100686142  calcitonin receptor-stimulating peptide 2-like [KO:K12332]
403817  ADM; pro-adrenomedullin precursor [KO:K12333]
606919  ADM2; protein ADM2 isoform X5 [KO:K25343]
488438  CALCRL; calcitonin gene-related peptide type 1 receptor [KO:K04577]
607163  RAMP1; receptor activity-modifying protein 1 [KO:K08447]
480515  RAMP2; receptor activity-modifying protein 2 isoform X1 [KO:K08448]
100855938  RAMP3; receptor activity-modifying protein 3 isoform X1 [KO:K08449]
403943  GNAS; guanine nucleotide-binding protein G(s) subunit alpha [KO:K04632]
607357  ADCY1; LOW QUALITY PROTEIN: adenylate cyclase type 1 isoform X5 [KO:K08041] [EC:4.6.1.1]
478624  ADCY2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
482994  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
480271  ADCY4; adenylate cyclase type 4 isoform X2 [KO:K08044] [EC:4.6.1.1]
403859  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
477625  ADCY6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
487289  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
482045  ADCY8; adenylate cyclase type 8 isoform X2 [KO:K08048] [EC:4.6.1.1]
490031  ADCY9; adenylate cyclase type 9 isoform X2 [KO:K08049] [EC:4.6.1.1]
403556  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
479975  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X2 [KO:K04345] [EC:2.7.11.11]
608289  NPPA; natriuretic peptides A precursor [KO:K12334]
487441  NPPB; natriuretic peptides B [KO:K12335]
490455  NPR1; atrial natriuretic peptide receptor 1 [KO:K12323] [EC:4.6.1.2]
610169  NPPC; C-type natriuretic peptide [KO:K12336]
474762  NPR2; atrial natriuretic peptide receptor 2 isoform X1 [KO:K12324] [EC:4.6.1.2]
609616  PRKG1; cGMP-dependent protein kinase 1 isoform X3 [KO:K07376] [EC:2.7.11.12]
100855453  IRAG1; inositol 1,4,5-triphosphate receptor associated 1 isoform X3 [KO:K12337]
479455  GUCY1A2; guanylate cyclase soluble subunit alpha-2 isoform X3 [KO:K12318] [EC:4.6.1.2]
482663  GUCY1A1; guanylate cyclase soluble subunit alpha-1 [KO:K12318] [EC:4.6.1.2]
485435  guanylate cyclase soluble subunit beta-2-like [KO:K12319] [EC:4.6.1.2]
553102  GUCY1B1; guanylate cyclase soluble subunit beta-1 [KO:K12319] [EC:4.6.1.2]
Compound
C00076  Calcium cation
C00165  Diacylglycerol
C00212  Adenosine
C00219  Arachidonate
C00238  Potassium cation
C00533  Nitric oxide
C00547  L-Noradrenaline
C00575  3',5'-Cyclic AMP
C00942  3',5'-Cyclic GMP
C01245  D-myo-Inositol 1,4,5-trisphosphate
C01312  Prostaglandin I2
C14748  20-HETE
C14768  5,6-EET
C14769  8,9-EET
C14770  11,12-EET
C14771  14,15-EET
Reference
PMID:17458653
  Authors
Akata T
  Title
Cellular and molecular mechanisms regulating vascular tone. Part 2: regulatory mechanisms modulating Ca2+ mobilization and/or myofilament Ca2+ sensitivity in vascular smooth muscle cells.
  Journal
J Anesth 21:232-42 (2007)
DOI:10.1007/s00540-006-0488-4
Reference
PMID:12689814
  Authors
Ogut O, Brozovich FV
  Title
Regulation of force in vascular smooth muscle.
  Journal
J Mol Cell Cardiol 35:347-55 (2003)
DOI:10.1016/S0022-2828(03)00045-2
Reference
PMID:16339747
  Authors
Hilgers RH, Webb RC
  Title
Molecular aspects of arterial smooth muscle contraction: focus on Rho.
  Journal
Exp Biol Med (Maywood) 230:829-35 (2005)
DOI:10.1177/153537020523001107
Reference
PMID:12693609
  Authors
Schlossmann J, Feil R, Hofmann F
  Title
Signaling through NO and cGMP-dependent protein kinases.
  Journal
Ann Med 35:21-7 (2003)
DOI:10.1080/07853890310004093
Reference
PMID:16870827
  Authors
Mehta PK, Griendling KK
  Title
Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system.
  Journal
Am J Physiol Cell Physiol 292:C82-97 (2007)
DOI:10.1152/ajpcell.00287.2006
Reference
PMID:19120701
  Authors
Kim HR, Appel S, Vetterkind S, Gangopadhyay SS, Morgan KG
  Title
Smooth muscle signalling pathways in health and disease.
  Journal
J Cell Mol Med 12:2165-80 (2008)
DOI:10.1111/j.1582-4934.2008.00552.x
Reference
PMID:11165670
  Authors
Fukata Y, Amano M, Kaibuchi K
  Title
Rho-Rho-kinase pathway in smooth muscle contraction and cytoskeletal reorganization of non-muscle cells.
  Journal
Trends Pharmacol Sci 22:32-9 (2001)
DOI:10.1016/S0165-6147(00)01596-0
Reference
PMID:17158339
  Authors
Dimopoulos GJ, Semba S, Kitazawa K, Eto M, Kitazawa T
  Title
Ca2+-dependent rapid Ca2+ sensitization of contraction in arterial smooth muscle.
  Journal
Circ Res 100:121-9 (2007)
DOI:10.1161/01.RES.0000253902.90489.df
Reference
PMID:17200683
  Authors
Hynynen MM, Khalil RA
  Title
The vascular endothelin system in hypertension--recent patents and discoveries.
  Journal
Recent Pat Cardiovasc Drug Discov 1:95-108 (2006)
DOI:10.2174/157489006775244263
Reference
PMID:15269340
  Authors
Brain SD, Grant AD
  Title
Vascular actions of calcitonin gene-related peptide and adrenomedullin.
  Journal
Physiol Rev 84:903-34 (2004)
DOI:10.1152/physrev.00037.2003
Reference
PMID:11773611
  Authors
Roman RJ
  Title
P-450 metabolites of arachidonic acid in the control of cardiovascular function.
  Journal
Physiol Rev 82:131-85 (2002)
DOI:10.1152/physrev.00021.2001
Reference
PMID:18040024
  Authors
Surks HK
  Title
cGMP-dependent protein kinase I and smooth muscle relaxation: a tale of two isoforms.
  Journal
Circ Res 101:1078-80 (2007)
DOI:10.1161/CIRCRESAHA.107.165779
Reference
PMID:15026027
  Authors
Vanhoutte PM
  Title
Endothelium-dependent hyperpolarizations: the history.
  Journal
Pharmacol Res 49:503-8 (2004)
DOI:10.1016/j.phrs.2003.11.015
Reference
PMID:10221985
  Authors
Davis MJ, Hill MA
  Title
Signaling mechanisms underlying the vascular myogenic response.
  Journal
Physiol Rev 79:387-423 (1999)
DOI:10.1152/physrev.1999.79.2.387
Reference
PMID:11679404
  Authors
Fleming I.
  Title
Cytochrome p450 and vascular homeostasis.
  Journal
Circ Res 89:753-62 (2001)
DOI:10.1161/hh2101.099268
Reference
PMID:10911373
  Authors
Carvajal JA, Germain AM, Huidobro-Toro JP, Weiner CP
  Title
Molecular mechanism of cGMP-mediated smooth muscle relaxation.
  Journal
J Cell Physiol 184:409-20 (2000)
DOI:10.1002/1097-4652(200009)184:3<409::AID-JCP16>3.0.CO;2-K
Reference
PMID:18552454
  Authors
Ko EA, Han J, Jung ID, Park WS
  Title
Physiological roles of K+ channels in vascular smooth muscle cells.
  Journal
J Smooth Muscle Res 44:65-81 (2008)
DOI:10.1540/jsmr.44.65
Reference
PMID:18703404
  Authors
Woodard GE, Rosado JA
  Title
Natriuretic peptides in vascular physiology and pathology.
  Journal
Int Rev Cell Mol Biol 268:59-93 (2008)
DOI:10.1016/S1937-6448(08)00803-4
Reference
PMID:11709400
  Authors
Berry C, Touyz R, Dominiczak AF, Webb RC, Johns DG
  Title
Angiotensin receptors: signaling, vascular pathophysiology, and interactions with ceramide.
  Journal
Am J Physiol Heart Circ Physiol 281:H2337-65 (2001)
DOI:10.1152/ajpheart.2001.281.6.H2337
Reference
PMID:15725705
  Authors
Hirano K, Hirano M, Kanaide H
  Title
Regulation of myosin phosphorylation and myofilament Ca2+ sensitivity in vascular smooth muscle.
  Journal
J Smooth Muscle Res 40:219-36 (2004)
DOI:10.1540/jsmr.40.219
Reference
PMID:9458738
  Authors
Freeman EJ, Ruehr ML, Dorman RV
  Title
ANG II-induced translocation of cytosolic PLA2 to the nucleus in vascular smooth muscle cells.
  Journal
Am J Physiol 274:C282-8 (1998)
DOI:10.1152/ajpcell.1998.274.1.C282
Reference
PMID:12060106
  Authors
Murphy TV, Spurrell BE, Hill MA
  Title
Cellular signalling in arteriolar myogenic constriction: involvement of tyrosine phosphorylation pathways.
  Journal
Clin Exp Pharmacol Physiol 29:612-9 (2002)
DOI:10.1046/j.1440-1681.2002.03698.x
Related
pathway
cfa00590  Arachidonic acid metabolism
cfa04020  Calcium signaling pathway
KO pathway
ko04270   
LinkDB

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