KEGG   PATHWAY: ko04270Help
Entry
ko04270                     Pathway                                

Name
Vascular smooth muscle contraction
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
BRITE hierarchy
Pathway map
Vascular smooth muscle contraction
ko04270

All organismsOrtholog table
Disease
H00728  
Brugada syndrome (BRS)
H00731  
Atrial fibrillation
H00746  
Hypokalemic periodic paralysis (HypoPP)
H00801  
Familial thoracic aortic aneurysm and dissection (TAAD)
H01258  
Generalized epilepsy and paroxysmal dyskinesia (GEPD)
Other DBs
BSID: 
GO: 
Orthology
K04135  
adrenergic receptor alpha-1A
K04136  
adrenergic receptor alpha-1B
K04137  
adrenergic receptor alpha-1D
K04166  
angiotensin II receptor type 1
K04197  
endothelin receptor type A
K04226  
arginine vasopressin receptor 1A
K04227  
arginine vasopressin receptor 1B
K04634  
guanine nucleotide-binding protein G(q) subunit alpha
K04635  
guanine nucleotide-binding protein subunit alpha-11
K01047  
secretory phospholipase A2 [EC:3.1.1.4]
K16342  
cytosolic phospholipase A2 [EC:3.1.1.4]
K16343  
calcium-independent phospholipase A2 [EC:3.1.1.4]
K17687  
alkane 1-monooxygenase [EC:1.14.15.3]
K17688  
alkane 1-monooxygenase [EC:1.14.15.3]
K07425  
alkane 1-monooxygenase [EC:1.14.15.3]
K04936  
potassium large conductance calcium-activated channel subfamily M alpha member 1
K05274  
potassium large conductance calcium-activated channel subfamily M alpha member 3
K04937  
potassium large conductance calcium-activated channel subfamily M beta member 1
K04938  
potassium large conductance calcium-activated channel subfamily M beta member 2
K04939  
potassium large conductance calcium-activated channel subfamily M beta member 3
K04941  
potassium large conductance calcium-activated channel subfamily M beta member 4
K04850  
voltage-dependent calcium channel L type alpha-1C
K04851  
voltage-dependent calcium channel L type alpha-1D
K04853  
voltage-dependent calcium channel L type alpha-1F
K04857  
voltage-dependent calcium channel L type alpha-1S
K02183  
calmodulin
K00907  
myosin-light-chain kinase [EC:2.7.11.18]
K12751  
myosin light chain 6
K12755  
myosin regulatory light chain 9
K05858  
phosphatidylinositol phospholipase C, beta [EC:3.1.4.11]
K04958  
inositol 1,4,5-triphosphate receptor type 1
K04959  
inositol 1,4,5-triphosphate receptor type 2
K04960  
inositol 1,4,5-triphosphate receptor type 3
K02677  
classical protein kinase C [EC:2.7.11.13]
K06068  
novel protein kinase C delta type [EC:2.7.11.13]
K18050  
novel protein kinase C epsilon type [EC:2.7.11.13]
K18051  
novel protein kinase C eta type [EC:2.7.11.13]
K18052  
novel protein kinase C theta type [EC:2.7.11.13]
K08845  
A-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]
K04365  
B-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]
K04366  
RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]
K04368  
mitogen-activated protein kinase kinase 1 [EC:2.7.12.2]
K04369  
mitogen-activated protein kinase kinase 2 [EC:2.7.12.2]
K04371  
mitogen-activated protein kinase 1/3 [EC:2.7.11.24]
K12327  
caldesmon
K12313  
actin, aortic smooth muscle
K12315  
actin, gamma-enteric smooth muscle
K12328  
protein phosphatase 1 regulatory subunit 14A
K06269  
serine/threonine-protein phosphatase PP1 catalytic subunit [EC:3.1.3.16]
K06270  
protein phosphatase 1 regulatory subunit 12A
K12329  
protein phosphatase 1 regulatory subunit 12B
K17457  
protein phosphatase 1 regulatory subunit 12C
K04346  
guanine nucleotide-binding protein subunit alpha-12
K04639  
guanine nucleotide-binding protein subunit alpha-13
K07532  
Rho guanine nucleotide exchange factor 12
K12330  
Rho guanine nucleotide exchange factor 1
K12331  
Rho guanine nucleotide exchange factor 11
K04513  
Ras homolog gene family, member A
K04514  
Rho-associated protein kinase 1 [EC:2.7.11.1]
K17388  
Rho-associated protein kinase 2 [EC:2.7.11.1]
K04266  
adenosine receptor A2a
K04267  
adenosine receptor A2b
K04263  
prostacyclin receptor
K04577  
calcitonin receptor-like
K08447  
receptor activity modifying protein 1
K08448  
receptor activity modifying protein 2
K08449  
receptor activity modifying protein 3
K04632  
guanine nucleotide-binding protein G(s) subunit alpha
K08041  
adenylate cyclase 1 [EC:4.6.1.1]
K08042  
adenylate cyclase 2 [EC:4.6.1.1]
K08043  
adenylate cyclase 3 [EC:4.6.1.1]
K08044  
adenylate cyclase 4 [EC:4.6.1.1]
K08045  
adenylate cyclase 5 [EC:4.6.1.1]
K08046  
adenylate cyclase 6 [EC:4.6.1.1]
K08047  
adenylate cyclase 7 [EC:4.6.1.1]
K08048  
adenylate cyclase 8 [EC:4.6.1.1]
K08049  
adenylate cyclase 9 [EC:4.6.1.1]
K04345  
protein kinase A [EC:2.7.11.11]
K12323  
atrial natriuretic peptide receptor A [EC:4.6.1.2]
K12324  
atrial natriuretic peptide receptor B [EC:4.6.1.2]
K12337  
inositol 1,4,5-triphosphate receptor-associated cGMP kinase substrate
K12318  
guanylate cyclase soluble subunit alpha [EC:4.6.1.2]
K12319  
guanylate cyclase soluble subunit beta [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
C02135  
Angiotensin II
C13662  
Arg-vasopressin
C14748  
20-HETE
C14768  
5,6-EET
C14769  
8,9-EET
C14770  
11,12-EET
C14771  
14,15-EET
C16003  
Atrial natriuretic peptide
C16004  
Brain natriuretic peptide
C16005  
C-Type natriuretic peptide
C16010  
Endothelin-1
C16012  
Endothelin-2
C16013  
Endothelin-3
C16125  
Calcitonin gene-related peptide 1
C16127  
Adrenomedullin
Reference
  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)
Reference
  Authors
Ogut O, Brozovich FV
  Title
Regulation of force in vascular smooth muscle.
  Journal
J Mol Cell Cardiol 35:347-55 (2003)
Reference
  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)
Reference
  Authors
Schlossmann J, Feil R, Hofmann F
  Title
Signaling through NO and cGMP-dependent protein kinases.
  Journal
Ann Med 35:21-7 (2003)
Reference
  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)
Reference
  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)
Reference
  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)
Reference
  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)
Reference
  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)
Reference
  Authors
Brain SD, Grant AD
  Title
Vascular actions of calcitonin gene-related peptide and adrenomedullin.
  Journal
Physiol Rev 84:903-34 (2004)
Reference
  Authors
Roman RJ
  Title
P-450 metabolites of arachidonic acid in the control of cardiovascular function.
  Journal
Physiol Rev 82:131-85 (2002)
Reference
  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)
Reference
  Authors
Vanhoutte PM
  Title
Endothelium-dependent hyperpolarizations: the history.
  Journal
Pharmacol Res 49:503-8 (2004)
Reference
  Authors
Davis MJ, Hill MA
  Title
Signaling mechanisms underlying the vascular myogenic response.
  Journal
Physiol Rev 79:387-423 (1999)
Reference
  Authors
Fleming I.
  Title
Cytochrome p450 and vascular homeostasis.
  Journal
Circ Res 89:753-62 (2001)
Reference
  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)
Reference
  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)
Reference
  Authors
Woodard GE, Rosado JA
  Title
Natriuretic peptides in vascular physiology and pathology.
  Journal
Int Rev Cell Mol Biol 268:59-93 (2008)
Reference
  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)
Reference
  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)
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)
Reference
  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)

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