KEGG   PATHWAY: epz04270
Entry
epz04270                    Pathway                                
Name
Vascular smooth muscle contraction - Equus przewalskii (Przewalski's horse)
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
epz04270  Vascular smooth muscle contraction
epz04270

Other DBs
GO: 0014829
Organism
Equus przewalskii (Przewalski's horse) [GN:epz]
Gene
103561082  ADRA1A; adrenoceptor alpha 1A [KO:K04135]
103553004  ADRA1B; adrenoceptor alpha 1B [KO:K04136]
103550747  ADRA1D; adrenoceptor alpha 1D [KO:K04137]
103561130  AGT; angiotensinogen [KO:K09821]
103558752  AGTR1; angiotensin II receptor type 1 [KO:K04166]
103552897  EDN1; endothelin 1 [KO:K16366]
103553551  EDN2; endothelin 2 [KO:K16367]
103554763  EDN3; endothelin 3 [KO:K05227]
103555691  EDNRA; endothelin receptor type A [KO:K04197]
103552372  AVPR1A; arginine vasopressin receptor 1A [KO:K04226]
103553836  AVPR1B; arginine vasopressin receptor 1B [KO:K04227]
103553450  GNAQ; G protein subunit alpha q [KO:K04634]
103543382  guanine nucleotide-binding protein subunit alpha-11-like [KO:K04635]
103550322  PLA2G2E; phospholipase A2 group IIE [KO:K01047] [EC:3.1.1.4]
103550324  PLA2G5; phospholipase A2 group V [KO:K01047] [EC:3.1.1.4]
103550325  PLA2G2A; phospholipase A2 group IIA [KO:K01047] [EC:3.1.1.4]
103550326  PLA2G2D; phospholipase A2 group IID [KO:K01047] [EC:3.1.1.4]
103550327  PLA2G2F; phospholipase A2 group IIF [KO:K01047] [EC:3.1.1.4]
103550328  PLA2G2C; phospholipase A2 group IIC [KO:K01047] [EC:3.1.1.4]
103540599  PLA2G1B; phospholipase A2 group IB [KO:K01047] [EC:3.1.1.4]
103551247  phospholipase A2-like [KO:K01047] [EC:3.1.1.4]
103551166  PLA2G10; phospholipase A2 group X [KO:K01047] [EC:3.1.1.4]
103557869  group XIIB secretory phospholipase A2-like protein [KO:K01047] [EC:3.1.1.4]
103562390  PLA2G12A; phospholipase A2 group XIIA [KO:K01047] [EC:3.1.1.4]
103566938  PLA2G3; phospholipase A2 group III [KO:K01047] [EC:3.1.1.4]
103549946  PLA2G4D; phospholipase A2 group IVD [KO:K16342] [EC:3.1.1.4]
103549947  PLA2G4E; phospholipase A2 group IVE [KO:K16342] [EC:3.1.1.4]
103549950  PLA2G4B; phospholipase A2 group IVB [KO:K16342] [EC:3.1.1.4]
103549953  PLA2G4F; phospholipase A2 group IVF [KO:K16342] [EC:3.1.1.4]
103560072  PLA2G4A; phospholipase A2 group IVA [KO:K16342] [EC:3.1.1.4]
103565810  PLA2G6; phospholipase A2 group VI [KO:K16343] [EC:3.1.1.4]
103565698  cytochrome P450 4A11-like [KO:K07425] [EC:1.14.14.80]
103567431  cytochrome P450 4A11-like [KO:K07425] [EC:1.14.14.80]
103550311  KCNMA1; potassium calcium-activated channel subfamily M alpha 1 [KO:K04936]
103540740  KCNMB1; potassium calcium-activated channel subfamily M regulatory beta subunit 1 [KO:K04937]
103552562  KCNMB2; potassium calcium-activated channel subfamily M regulatory beta subunit 2 [KO:K04938]
103552224  KCNMB3; potassium calcium-activated channel subfamily M regulatory beta subunit 3 [KO:K04939]
103557406  KCNMB4; potassium calcium-activated channel subfamily M regulatory beta subunit 4 [KO:K04941]
103560754  voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851]
103543955  CACNA1F; calcium voltage-gated channel subunit alpha1 F [KO:K04853]
103565109  CACNA1S; calcium voltage-gated channel subunit alpha1 S [KO:K04857]
103548885  CALML5; calmodulin like 5 [KO:K02183]
103548886  CALML3; calmodulin like 3 [KO:K02183]
103549905  CALM1; calmodulin 1 [KO:K02183]
103558105  CALM2; calmodulin 2 [KO:K02183]
103564053  calmodulin-like protein 4 [KO:K02183]
103544963  calmodulin-alpha-like [KO:K02183]
103567415  CALML6; calmodulin like 6 [KO:K02183]
103548123  MYLK4; myosin light chain kinase family member 4 [KO:K00907] [EC:2.7.11.18]
103547465  MYLK; myosin light chain kinase [KO:K00907] [EC:2.7.11.18]
103559162  MYLK2; myosin light chain kinase 2 [KO:K00907] [EC:2.7.11.18]
103557557  MYL6; myosin light chain 6 [KO:K12751]
103557558  MYL6B; myosin light chain 6B [KO:K12751]
103557622  MYL9; myosin light chain 9 [KO:K12755]
103559082  MYH10; myosin heavy chain 10 [KO:K10352]
103563388  MYH9; myosin heavy chain 9 [KO:K10352]
103558095  MYH11; myosin heavy chain 11 [KO:K10352]
103558302  MYH14; myosin heavy chain 14 [KO:K10352]
103562440  PLCB1; phospholipase C beta 1 [KO:K05858] [EC:3.1.4.11]
103559733  PLCB4; phospholipase C beta 4 [KO:K05858] [EC:3.1.4.11]
103561633  PLCB2; phospholipase C beta 2 [KO:K05858] [EC:3.1.4.11]
103542193  PLCB3; phospholipase C beta 3 [KO:K05858] [EC:3.1.4.11]
103550297  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
103546630  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
103548182  inositol 1,4,5-trisphosphate receptor type 2-like [KO:K04959]
103564724  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
103558165  PRKCB; protein kinase C beta [KO:K19662] [EC:2.7.11.13]
103556196  PRKCG; protein kinase C gamma [KO:K19663] [EC:2.7.11.13]
103546514  PRKCD; protein kinase C delta [KO:K06068] [EC:2.7.11.13]
103549602  PRKCE; protein kinase C epsilon [KO:K18050] [EC:2.7.11.13]
103557199  PRKCH; protein kinase C eta [KO:K18051] [EC:2.7.11.13]
103557074  PRKCQ; protein kinase C theta [KO:K18052] [EC:2.7.11.13]
103555338  BRAF; B-Raf proto-oncogene, serine/threonine kinase [KO:K04365] [EC:2.7.11.1]
103554541  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
103549630  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
103543290  dual specificity mitogen-activated protein kinase kinase 2-like [KO:K04369] [EC:2.7.12.2]
103547261  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
103562408  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
103563103  CALD1; caldesmon 1 [KO:K12327]
103558122  ACTA2; actin, alpha 2, smooth muscle, aorta [KO:K12313]
103559860  ACTG2; actin, gamma 2, smooth muscle, enteric [KO:K12315]
103541445  PPP1R14A; protein phosphatase 1 regulatory inhibitor subunit 14A [KO:K12328]
103560150  PPP1CA; protein phosphatase 1 catalytic subunit alpha [KO:K06269] [EC:3.1.3.16]
103541647  PPP1CC; protein phosphatase 1 catalytic subunit gamma [KO:K06269] [EC:3.1.3.16]
103549472  PPP1CB; protein phosphatase 1 catalytic subunit beta [KO:K06269] [EC:3.1.3.16]
103549928  PPP1R12A; protein phosphatase 1 regulatory subunit 12A [KO:K06270]
103561986  PPP1R12B; protein phosphatase 1 regulatory subunit 12B [KO:K12329]
103562875  PPP1R12C; protein phosphatase 1 regulatory subunit 12C [KO:K17457]
103549418  GNA12; G protein subunit alpha 12 [KO:K04346]
103553497  GNA13; G protein subunit alpha 13 [KO:K04639]
103546845  ARHGEF12; Rho guanine nucleotide exchange factor 12 [KO:K07532]
103563986  ARHGEF1; Rho guanine nucleotide exchange factor 1 [KO:K12330]
103565257  ARHGEF11; Rho guanine nucleotide exchange factor 11 [KO:K12331]
103553409  RHOA; ras homolog family member A [KO:K04513]
103552805  ROCK1; Rho associated coiled-coil containing protein kinase 1 [KO:K04514] [EC:2.7.11.39]
103557393  ROCK2; Rho associated coiled-coil containing protein kinase 2 [KO:K17388] [EC:2.7.11.39]
103561852  ADORA2A; adenosine A2a receptor [KO:K04266]
103560476  ADORA2B; adenosine A2b receptor [KO:K04267]
103542501  PTGIR; prostaglandin I2 (prostacyclin) receptor (IP) [KO:K04263]
103557933  calcitonin gene-related peptide 1 [KO:K12332]
103557935  calcitonin gene-related peptide 1-like [KO:K12332]
103565273  calcitonin gene-related peptide 2 [KO:K12332]
103559917  ADM; adrenomedullin [KO:K12333]
103564759  ADM2; adrenomedullin 2 [KO:K25343]
103549924  CALCRL; calcitonin receptor like receptor [KO:K04577]
103557369  RAMP1; receptor activity modifying protein 1 [KO:K08447]
103550350  RAMP2; receptor activity modifying protein 2 [KO:K08448]
103555919  RAMP3; receptor activity modifying protein 3 [KO:K08449]
103565402  guanine nucleotide-binding protein G(s) subunit alpha [KO:K04632]
103547036  neuroendocrine secretory protein 55 [KO:K04632]
103550430  ADCY1; adenylate cyclase 1 [KO:K08041] [EC:4.6.1.1]
103562505  adenylate cyclase type 2-like [KO:K08042] [EC:4.6.1.1]
103547823  ADCY3; adenylate cyclase 3 [KO:K08043] [EC:4.6.1.1]
103561050  ADCY4; adenylate cyclase 4 [KO:K08044] [EC:4.6.1.1]
103563830  ADCY5; adenylate cyclase 5 [KO:K08045] [EC:4.6.1.1]
103563634  ADCY6; adenylate cyclase 6 [KO:K08046] [EC:4.6.1.1]
103556685  ADCY7; adenylate cyclase 7 [KO:K08047] [EC:4.6.1.1]
103565019  adenylate cyclase type 8-like [KO:K08048] [EC:4.6.1.1]
103567623  ADCY8; adenylate cyclase 8 [KO:K08048] [EC:4.6.1.1]
103553014  ADCY9; adenylate cyclase 9 [KO:K08049] [EC:4.6.1.1]
103557289  PRKACB; protein kinase cAMP-activated catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
103565953  PRKACA; protein kinase cAMP-activated catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
103552182  NPPA; natriuretic peptide A [KO:K12334]
103552181  NPPB; natriuretic peptide B [KO:K12335]
103566725  NPR1; natriuretic peptide receptor 1 [KO:K12323] [EC:4.6.1.2]
103554834  NPPC; natriuretic peptide C [KO:K12336]
103541278  NPR2; natriuretic peptide receptor 2 [KO:K12324] [EC:4.6.1.2]
103542199  MRVI1; murine retrovirus integration site 1 homolog [KO:K12337]
103563826  guanylate cyclase soluble subunit alpha-2 [KO:K12318] [EC:4.6.1.2]
103562610  GUCY1A3; guanylate cyclase 1 soluble subunit alpha [KO:K12318] [EC:4.6.1.2]
103551994  guanylate cyclase soluble subunit beta-2-like [KO:K12319] [EC:4.6.1.2]
103562608  GUCY1B3; guanylate cyclase 1 soluble subunit beta [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
epz00590  Arachidonic acid metabolism
epz04020  Calcium signaling pathway
KO pathway
ko04270   
LinkDB

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