KEGG   PATHWAY: ocu04270
Entry
ocu04270                    Pathway                                
Name
Vascular smooth muscle contraction - Oryctolagus cuniculus (rabbit)
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
ocu04270  Vascular smooth muscle contraction
ocu04270

Other DBs
GO: 0014829
Organism
Oryctolagus cuniculus (rabbit) [GN:ocu]
Gene
100009237  ADRA1A; alpha-1A adrenergic receptor [KO:K04135]
100008731  ADRA1B; alpha-1B adrenergic receptor [KO:K04136]
100009398  ADRA1D; alpha-1D adrenergic receptor [KO:K04137]
100358371  angiotensinogen isoform X1 [KO:K09821]
100009164  AGTR1; type-1 angiotensin II receptor [KO:K04166]
100009270  EDN1; endothelin-1 precursor [KO:K16366]
100008634  EDN2; endothelin-2 precursor [KO:K16367]
100348609  endothelin-3 isoform X1 [KO:K05227]
100126073  EDNRA; endothelin-1 receptor precursor [KO:K04197]
100354268  vasopressin-neurophysin 2-copeptin [KO:K05242]
100345154  vasopressin V1a receptor [KO:K04226]
100354969  vasopressin V1b receptor [KO:K04227]
100340719  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
100358709  group XIIA secretory phospholipase A2 [KO:K01047] [EC:3.1.1.4]
100340856  group XIIB secretory phospholipase A2-like protein isoform X3 [KO:K01047] [EC:3.1.1.4]
100338271  group 3 secretory phospholipase A2 [KO:K01047] [EC:3.1.1.4]
100347180  phospholipase A2 [KO:K01047] [EC:3.1.1.4]
100342898  putative inactive group IIC secretory phospholipase A2 [KO:K01047] [EC:3.1.1.4]
100343150  group IIF secretory phospholipase A2 isoform X2 [KO:K01047] [EC:3.1.1.4]
100343408  group IID secretory phospholipase A2 [KO:K01047] [EC:3.1.1.4]
100343664  phospholipase A2 group V [KO:K01047] [EC:3.1.1.4]
100351425  phospholipase A2, membrane associated [KO:K01047] [EC:3.1.1.4]
100343913  phospholipase A2, membrane associated [KO:K01047] [EC:3.1.1.4]
100344421  phospholipase A2, membrane associated isoform X1 [KO:K01047] [EC:3.1.1.4]
100351928  group IIE secretory phospholipase A2 [KO:K01047] [EC:3.1.1.4]
100341685  group 10 secretory phospholipase A2 isoform X3 [KO:K01047] [EC:3.1.1.4]
100533118  PLA2G4B; cytosolic phospholipase A2 beta [KO:K16342] [EC:3.1.1.4]
100340517  cytosolic phospholipase A2 zeta isoform X1 [KO:K16342] [EC:3.1.1.4]
100340775  cytosolic phospholipase A2 delta isoform X2 [KO:K16342] [EC:3.1.1.4]
100341033  PLA2G4E; cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]
100008748  PLA2G4A; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
100341237  cytosolic phospholipase A2 gamma isoform X1 [KO:K16342] [EC:3.1.1.4]
100008961  PLA2G6; 85/88 kDa calcium-independent phospholipase A2 [KO:K16343] [EC:3.1.1.4]
127490931  85/88 kDa calcium-independent phospholipase A2-like [KO:K16343] [EC:3.1.1.4]
100008745  KCNMA1; calcium-activated potassium channel subunit alpha-1 [KO:K04936]
103346203  potassium channel subfamily U member 1 isoform X1 [KO:K05274]
100009034  KCNMB1; calcium-activated potassium channel subunit beta-1 [KO:K04937]
100344926  calcium-activated potassium channel subunit beta-2 isoform X2 [KO:K04938]
100345697  LOW QUALITY PROTEIN: calcium-activated potassium channel subunit beta-3 [KO:K04939]
100342622  calcium-activated potassium channel subunit beta-4 isoform X2 [KO:K04941]
100101555  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C [KO:K04850]
100327259  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
100357261  voltage-dependent L-type calcium channel subunit alpha-1F [KO:K04853]
100009585  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
103345165  LOW QUALITY PROTEIN: calmodulin-like protein 3 [KO:K02183]
100347856  calmodulin-like protein 3 [KO:K02183]
100354905  calmodulin-3 [KO:K02183]
100352392  CALM2; calmodulin [KO:K02183]
100350107  calmodulin-1 [KO:K02183]
100345526  calmodulin-like protein 4 isoform X1 [KO:K02183]
100009051  MYLK2; myosin light chain kinase 2, skeletal/cardiac muscle [KO:K00907] [EC:2.7.11.18]
100353972  myosin light chain kinase family member 4 isoform X1 [KO:K00907] [EC:2.7.11.18]
100348694  myosin light chain kinase 3 isoform X1 [KO:K00907] [EC:2.7.11.18]
127493971  myosin light chain kinase, smooth muscle [KO:K00907] [EC:2.7.11.18]
100355039  myosin light polypeptide 6-like [KO:K12751]
103348296  myosin light chain 6B isoform X1 [KO:K12751]
100349824  myosin light polypeptide 6 isoform X3 [KO:K12751]
108176653  myosin light polypeptide 6 isoform X1 [KO:K12751]
127487399  myosin light chain 6B isoform X1 [KO:K12751]
100343384  myosin regulatory light polypeptide 9 [KO:K12755]
100009001  myosin-9 [KO:K10352]
100009002  myosin-10 isoform X3 [KO:K10352]
100009145  MYH11; myosin-11 [KO:K10352]
100348672  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X4 [KO:K05858] [EC:3.1.4.11]
100350395  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
100341512  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X2 [KO:K05858] [EC:3.1.4.11]
103347536  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
100009505  inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
100356806  inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
100008939  inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
100037720  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
100037719  PRKCB; protein kinase C beta type isoform I [KO:K19662] [EC:2.7.11.13]
100009102  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
100008966  protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
100009103  PRKCE; protein kinase C epsilon type [KO:K18050] [EC:2.7.11.13]
100344184  protein kinase C eta type [KO:K18051] [EC:2.7.11.13]
103350889  protein kinase C theta type isoform X1 [KO:K18052] [EC:2.7.11.13]
100340437  serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
100351964  serine/threonine-protein kinase B-raf isoform X6 [KO:K04365] [EC:2.7.11.1]
100347407  RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
100009316  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
127489461  LOW QUALITY PROTEIN: dual specificity mitogen-activated protein kinase kinase 1-like [KO:K04368] [EC:2.7.12.2]
100347345  mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
100348561  mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100009077  CALD1; caldesmon [KO:K12327]
100009271  ACTA2; actin, aortic smooth muscle [KO:K12313]
100350318  actin, gamma-enteric smooth muscle [KO:K12315]
103348434  protein phosphatase 1 regulatory subunit 14A [KO:K12328]
100009587  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
100009298  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
100353054  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
100350558  protein phosphatase 1 regulatory subunit 12A isoform X1 [KO:K06270]
100356902  protein phosphatase 1 regulatory subunit 12B isoform X8 [KO:K12329]
100347293  guanine nucleotide-binding protein subunit alpha-12 [KO:K04346]
100352794  guanine nucleotide-binding protein subunit alpha-13 [KO:K04639]
100340118  rho guanine nucleotide exchange factor 12 isoform X1 [KO:K07532]
103347573  rho guanine nucleotide exchange factor 1 isoform X1 [KO:K12330]
100337815  rho guanine nucleotide exchange factor 11 isoform X1 [KO:K12331]
100356250  transforming protein RhoA [KO:K04513]
100348967  transforming protein RhoA-like [KO:K04513]
100340661  transforming protein RhoA [KO:K04513]
100346856  LOW QUALITY PROTEIN: transforming protein RhoA [KO:K04513]
100343368  transforming protein RhoA-like [KO:K04513]
100343680  transforming protein RhoA-like [KO:K04513]
127489660  transforming protein RhoA-like [KO:K04513]
100009220  ROCK1; rho-associated protein kinase 1 [KO:K04514] [EC:2.7.11.1]
100346837  rho-associated protein kinase 2 isoform X1 [KO:K17388] [EC:2.7.11.1]
100339944  adenosine receptor A2a [KO:K04266]
100008951  ADORA2B; adenosine receptor A2b [KO:K04267]
100355165  prostacyclin receptor [KO:K04263]
100008770  calcitonin gene-related peptide 2 [KO:K12332]
100008771  calcitonin gene-related peptide 2 isoform X5 [KO:K12332]
127487662  calcitonin gene-related peptide 2 [KO:K12332]
127487667  calcitonin-like isoform X1 [KO:K12332]
100347461  pro-adrenomedullin isoform X1 [KO:K12333]
100354426  calcitonin gene-related peptide type 1 receptor [KO:K04577]
103346209  receptor activity-modifying protein 1 [KO:K08447]
100345708  receptor activity-modifying protein 2 [KO:K08448]
100008904  guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
100346323  neuroendocrine secretory protein 55 [KO:K04632]
103347035  adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
100009201  adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
100343958  adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
100346742  adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
100009315  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
100354934  adenylate cyclase type 6 isoform X8 [KO:K08046] [EC:4.6.1.1]
100357357  adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
100337882  adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
100340877  adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
100008815  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
100342212  cAMP-dependent protein kinase catalytic subunit beta isoform X3 [KO:K04345] [EC:2.7.11.11]
100009087  NPPA; natriuretic peptides A precursor [KO:K12334]
103352511  natriuretic peptides B isoform X1 [KO:K12335]
100343663  atrial natriuretic peptide receptor 1 [KO:K12323] [EC:4.6.1.2]
100344147  C-type natriuretic peptide [KO:K12336]
100356598  atrial natriuretic peptide receptor 2 isoform X1 [KO:K12324] [EC:4.6.1.2]
100008694  PRKG1; cGMP-dependent protein kinase 1 [KO:K07376] [EC:2.7.11.12]
100008940  IRAG1; inositol 1,4,5-triphosphate receptor associated 1 isoform X3 [KO:K12337]
100350099  GUCY1A1; guanylate cyclase soluble subunit alpha-1 isoform X1 [KO:K12318] [EC:4.6.1.2]
100357621  guanylate cyclase soluble subunit alpha-2 [KO:K12318] [EC:4.6.1.2]
100349851  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
ocu00590  Arachidonic acid metabolism
ocu04020  Calcium signaling pathway
KO pathway
ko04270   
LinkDB

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