KEGG   PATHWAY: npr04270
Entry
npr04270                    Pathway                                
Name
Vascular smooth muscle contraction - Nanorana parkeri (Xizang Plateau frog)
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
npr04270  Vascular smooth muscle contraction
npr04270

Other DBs
GO: 0014829
Organism
Nanorana parkeri (Xizang Plateau frog) [GN:npr]
Gene
108791007  alpha-1A adrenergic receptor-like [KO:K04135]
108788121  ADRA1B; alpha-1B adrenergic receptor [KO:K04136]
108796204  ADRA1D; alpha-1D adrenergic receptor [KO:K04137]
108797310  AGTR1; type-1 angiotensin II receptor [KO:K04166]
108794282  type-1 angiotensin II receptor-like [KO:K04166]
108798928  endothelin-1-like [KO:K16366]
108802667  EDN3; endothelin-3 isoform X1 [KO:K05227]
108802629  EDNRA; endothelin-1 receptor [KO:K04197]
108798889  vasotocin-neurophysin VT [KO:K05242]
108798284  vasopressin V1a receptor-like [KO:K04226]
108790948  AVPR1B; vasopressin V1b receptor [KO:K04227]
108788493  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
108791250  GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
108797108  phospholipase A2 homolog otoconin-22-like [KO:K01047] [EC:3.1.1.4]
108798204  PLA2G12A; group XIIA secretory phospholipase A2 [KO:K01047] [EC:3.1.1.4]
108799534  PLA2G12B; group XIIB secretory phospholipase A2-like protein isoform X1 [KO:K01047] [EC:3.1.1.4]
108791727  group 10 secretory phospholipase A2-like [KO:K01047] [EC:3.1.1.4]
108801127  phospholipase A2, minor isoenzyme-like [KO:K01047] [EC:3.1.1.4]
108785849  PROCA1; protein PROCA1 [KO:K01047] [EC:3.1.1.4]
108787770  PLA2G1B; phospholipase A2 [KO:K01047] [EC:3.1.1.4]
108786243  PLA2G3; group 3 secretory phospholipase A2 [KO:K01047] [EC:3.1.1.4]
108798704  PLA2G4A; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
108789917  cytosolic phospholipase A2 delta-like [KO:K16342] [EC:3.1.1.4]
108793921  cytosolic phospholipase A2 delta-like [KO:K16342] [EC:3.1.1.4]
108789293  PLA2G4F; cytosolic phospholipase A2 zeta [KO:K16342] [EC:3.1.1.4]
108799210  PLA2G6; 85/88 kDa calcium-independent phospholipase A2 [KO:K16343] [EC:3.1.1.4]
108788403  KCNMA1; calcium-activated potassium channel subunit alpha-1 [KO:K04936]
108795125  KCNMB1; calcium-activated potassium channel subunit beta-1 [KO:K04937]
108785758  KCNMB2; calcium-activated potassium channel subunit beta-2 [KO:K04938]
108785757  KCNMB3; calcium-activated potassium channel subunit beta-3 isoform X1 [KO:K04939]
108804555  KCNMB4; calcium-activated potassium channel subunit beta-4 [KO:K04941]
108791575  voltage-dependent L-type calcium channel subunit alpha-1C-like isoform X1 [KO:K04850]
108786047  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851]
108788491  LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1F-like [KO:K04853]
108804869  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
108799395  calmodulin-alpha-like [KO:K02183]
108784100  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
108804514  CALM2; calmodulin [KO:K02183]
108788690  CALM1; calmodulin isoform X1 [KO:K02183]
108802964  MYLK3; myosin light chain kinase 3 [KO:K00907] [EC:2.7.11.18]
108787381  MYLK4; myosin light chain kinase family member 4 [KO:K00907] [EC:2.7.11.18]
108785969  myosin light chain kinase, smooth muscle-like [KO:K00907] [EC:2.7.11.18]
108790528  myosin light polypeptide 6-like isoform X1 [KO:K12751]
108787984  MYL9; myosin regulatory light polypeptide 9 [KO:K12755]
108789546  myosin-10-like isoform X1 [KO:K10352]
108793304  MYH11; myosin-11 isoform X1 [KO:K10352]
108793694  MYH9; myosin-9 [KO:K10352]
108795684  MYH10; myosin-10 [KO:K10352]
108789286  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
108793965  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
108795563  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
108795338  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
108791910  ITPR1; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
108786728  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
108787281  ITPR3; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
108791355  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
108797498  PRKCG; protein kinase C gamma type isoform X1 [KO:K19663] [EC:2.7.11.13]
108797915  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
108804505  PRKCE; protein kinase C epsilon type [KO:K18050] [EC:2.7.11.13]
108792059  PRKCH; protein kinase C eta type [KO:K18051] [EC:2.7.11.13]
108794777  PRKCQ; protein kinase C theta type isoform X1 [KO:K18052] [EC:2.7.11.13]
108801347  ARAF; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
108793029  BRAF; serine/threonine-protein kinase B-raf [KO:K04365] [EC:2.7.11.1]
108787573  RAF proto-oncogene serine/threonine-protein kinase-like [KO:K04366] [EC:2.7.11.1]
108784101  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
108794889  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
108788350  CALD1; caldesmon [KO:K12327]
108788870  ACTA2; actin, aortic smooth muscle [KO:K12313]
108792247  PPP1R14A; protein phosphatase 1 regulatory subunit 14A [KO:K12328]
108796512  serine/threonine-protein phosphatase alpha-2 isoform-like [KO:K06269] [EC:3.1.3.16]
108786345  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
108788527  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
108799788  PPP1R12A; protein phosphatase 1 regulatory subunit 12A [KO:K06270]
108802992  GNA13; guanine nucleotide-binding protein subunit alpha-13 isoform X1 [KO:K04639]
108796163  ARHGEF12; rho guanine nucleotide exchange factor 12 [KO:K07532]
108785651  ARHGEF1; rho guanine nucleotide exchange factor 1 [KO:K12330]
108796768  ARHGEF11; rho guanine nucleotide exchange factor 11 isoform X1 [KO:K12331]
108789229  transforming protein RhoA [KO:K04513]
108790560  rho-related GTP-binding protein RhoA-D isoform X1 [KO:K04513]
108797185  ROCK1; rho-associated protein kinase 1 [KO:K04514] [EC:2.7.11.1]
108788599  ROCK2; rho-associated protein kinase 2 isoform X1 [KO:K17388] [EC:2.7.11.1]
108787795  ADORA2A; adenosine receptor A2a isoform X1 [KO:K04266]
108790722  ADORA2B; adenosine receptor A2b [KO:K04267]
108803129  PTGIR; prostacyclin receptor [KO:K04263]
108802411  calcitonin-like isoform X1 [KO:K12332]
108785733  ADM; ADM [KO:K12333]
108802697  CALCRL; calcitonin gene-related peptide type 1 receptor [KO:K04577]
108789835  RAMP1; receptor activity-modifying protein 1 [KO:K08447]
108799824  RAMP3; receptor activity-modifying protein 3 [KO:K08449]
108802775  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoform X1 [KO:K04632]
108784456  guanine nucleotide-binding protein G(s) subunit alpha-like [KO:K04632]
108796974  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
108795542  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
108788450  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
108801019  adenylate cyclase type 5-like [KO:K08045] [EC:4.6.1.1]
108802250  adenylate cyclase type 6-like [KO:K08046] [EC:4.6.1.1]
108794932  ADCY7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
108788952  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
108790811  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
108784350  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
108790539  cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
108799429  natriuretic peptides A [KO:K12334]
108799421  natriuretic peptides A-like [KO:K12334]
108795208  NPR1; atrial natriuretic peptide receptor 1 isoform X1 [KO:K12323] [EC:4.6.1.2]
108799427  C-type natriuretic peptide 1 [KO:K12336]
108803119  C-type natriuretic peptide-like [KO:K12336]
108792489  NPPC; C-type natriuretic peptide [KO:K12336]
108803575  atrial natriuretic peptide receptor 2-like [KO:K12324] [EC:4.6.1.2]
108791371  atrial natriuretic peptide receptor 1-like [KO:K12324] [EC:4.6.1.2]
108797031  PRKG1; cGMP-dependent protein kinase 1 isoform X1 [KO:K07376] [EC:2.7.11.12]
108785922  MRVI1; protein MRVI1 [KO:K12337]
108789645  GUCY1A3; guanylate cyclase soluble subunit alpha-3 [KO:K12318] [EC:4.6.1.2]
108798037  guanylate cyclase soluble subunit alpha-2-like [KO:K12318] [EC:4.6.1.2]
108789639  GUCY1B3; guanylate cyclase soluble subunit beta-1 [KO:K12319] [EC:4.6.1.2]
108786354  guanylate cyclase soluble subunit beta-2-like [KO:K12319] [EC:4.6.1.2]
108787012  guanylate cyclase soluble subunit beta-2-like [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
npr00590  Arachidonic acid metabolism
npr04020  Calcium signaling pathway
KO pathway
ko04270   
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