Entry
Name
Vascular smooth muscle contraction - Loxodonta africana (African savanna elephant)
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
lav04270 Vascular smooth muscle contraction
Other DBs
Organism
Loxodonta africana (African savanna elephant) [GN:
lav ]
Gene
100656201 KCNMA1; calcium-activated potassium channel subunit alpha-1 isoform X6 [KO:K04936 ]
100656672 GNAQ; guanine nucleotide-binding protein G(q) subunit alpha isoform X1 [KO:K04634 ]
100657662 KCNMB3; calcium-activated potassium channel subunit beta-3 isoform X3 [KO:K04939 ]
100658510 KCNMB2; calcium-activated potassium channel subunit beta-2 [KO:K04938 ]
100659377 PPP1R14A; protein phosphatase 1 regulatory subunit 14A [KO:K12328 ]
100659666 ITPR3; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960 ]
100659992 CACNA1D; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851 ]
100661002 ARHGEF12; rho guanine nucleotide exchange factor 12 isoform X1 [KO:K07532 ]
100663278 KCNMB1; calcium-activated potassium channel subunit beta-1 [KO:K04937 ]
100663829 PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858 ] [EC:3.1.4.11 ]
100664965 GNA13; guanine nucleotide-binding protein subunit alpha-13 [KO:K04639 ]
100665028 ITPR1; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958 ]
100668504 KCNMB4; calcium-activated potassium channel subunit beta-4 [KO:K04941 ]
100668575 PLCB2; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858 ] [EC:3.1.4.11 ]
100669550 PPP1R12C; LOW QUALITY PROTEIN: protein phosphatase 1 regulatory subunit 12C [KO:K17457 ]
100670617 PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X3 [KO:K05858 ] [EC:3.1.4.11 ]
100670968 CALCRL; LOW QUALITY PROTEIN: calcitonin gene-related peptide type 1 receptor [KO:K04577 ]
100672435 PLCB1; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858 ] [EC:3.1.4.11 ]
100673089 CACNA1S; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857 ]
100673301 ARHGEF11; rho guanine nucleotide exchange factor 11 isoform X1 [KO:K12331 ]
100673814 PPP1CA; LOW QUALITY PROTEIN: serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269 ] [EC:3.1.3.16 ]
100673922 PPP1R12A; protein phosphatase 1 regulatory subunit 12A isoform X2 [KO:K06270 ]
100674589 ARHGEF1; rho guanine nucleotide exchange factor 1 isoform X2 [KO:K12330 ]
100674649 CACNA1F; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1F [KO:K04853 ]
100675383 KCNU1; LOW QUALITY PROTEIN: potassium channel subfamily U member 1 [KO:K05274 ]
100675940 PPP1R12B; protein phosphatase 1 regulatory subunit 12B isoform X3 [KO:K12329 ]
100676444 GNA12; guanine nucleotide-binding protein subunit alpha-12 [KO:K04346 ]
Compound
C01245 D-myo-Inositol 1,4,5-trisphosphate
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
Reference
Authors
Ogut O, Brozovich FV
Title
Regulation of force in vascular smooth muscle.
Journal
Reference
Authors
Hilgers RH, Webb RC
Title
Molecular aspects of arterial smooth muscle contraction: focus on Rho.
Journal
Reference
Authors
Schlossmann J, Feil R, Hofmann F
Title
Signaling through NO and cGMP-dependent protein kinases.
Journal
Reference
Authors
Mehta PK, Griendling KK
Title
Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system.
Journal
Reference
Authors
Kim HR, Appel S, Vetterkind S, Gangopadhyay SS, Morgan KG
Title
Smooth muscle signalling pathways in health and disease.
Journal
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
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
Reference
Authors
Hynynen MM, Khalil RA
Title
The vascular endothelin system in hypertension--recent patents and discoveries.
Journal
Reference
Authors
Brain SD, Grant AD
Title
Vascular actions of calcitonin gene-related peptide and adrenomedullin.
Journal
Reference
Authors
Roman RJ
Title
P-450 metabolites of arachidonic acid in the control of cardiovascular function.
Journal
Reference
Authors
Surks HK
Title
cGMP-dependent protein kinase I and smooth muscle relaxation: a tale of two isoforms.
Journal
Reference
Authors
Vanhoutte PM
Title
Endothelium-dependent hyperpolarizations: the history.
Journal
Reference
Authors
Davis MJ, Hill MA
Title
Signaling mechanisms underlying the vascular myogenic response.
Journal
Reference
Authors
Fleming I.
Title
Cytochrome p450 and vascular homeostasis.
Journal
Reference
Authors
Carvajal JA, Germain AM, Huidobro-Toro JP, Weiner CP
Title
Molecular mechanism of cGMP-mediated smooth muscle relaxation.
Journal
Reference
Authors
Ko EA, Han J, Jung ID, Park WS
Title
Physiological roles of K+ channels in vascular smooth muscle cells.
Journal
Reference
Authors
Woodard GE, Rosado JA
Title
Natriuretic peptides in vascular physiology and pathology.
Journal
Reference
Authors
Berry C, Touyz R, Dominiczak AF, Webb RC, Johns DG
Title
Angiotensin receptors: signaling, vascular pathophysiology, and interactions with ceramide.
Journal
Reference
Authors
Hirano K, Hirano M, Kanaide H
Title
Regulation of myosin phosphorylation and myofilament Ca2+ sensitivity in vascular smooth muscle.
Journal
Reference
Authors
Freeman EJ, Ruehr ML, Dorman RV
Title
ANG II-induced translocation of cytosolic PLA2 to the nucleus in vascular smooth muscle cells.
Journal
Reference
Authors
Murphy TV, Spurrell BE, Hill MA
Title
Cellular signalling in arteriolar myogenic constriction: involvement of tyrosine phosphorylation pathways.
Journal
Related pathway
KO pathway