Entry
Name
Vascular smooth muscle contraction - Etheostoma spectabile (orangethroat darter)
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
esp04270 Vascular smooth muscle contraction
Ortholog table
Other DBs
Organism
Etheostoma spectabile (orangethroat darter) [GN:
esp ]
Gene
116704803 guanine nucleotide-binding protein G(q) subunit alpha-like isoform X1 [KO:K04634 ]
116689828 guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634 ]
116670588 guanine nucleotide-binding protein G(q) subunit alpha-like isoform X1 [KO:K04635 ]
116695435 guanine nucleotide-binding protein G(q) subunit alpha-like isoform X1 [KO:K04635 ]
116705702 calcium-activated potassium channel subunit alpha-1 isoform X1 [KO:K04936 ]
116671648 calcium-activated potassium channel subunit alpha-1 isoform X1 [KO:K04936 ]
116699205 calcium-activated potassium channel subunit beta-2-like [KO:K04938 ]
116695363 calcium-activated potassium channel subunit beta-2-like [KO:K04938 ]
116695652 calcium-activated potassium channel subunit beta-2-like [KO:K04938 ]
116699323 calcium-activated potassium channel subunit beta-3-like [KO:K04939 ]
116672836 voltage-dependent L-type calcium channel subunit alpha-1C-like isoform X1 [KO:K04850 ]
116692928 voltage-dependent L-type calcium channel subunit alpha-1D-like isoform X1 [KO:K04851 ]
116687621 LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1D-like [KO:K04851 ]
116692878 voltage-dependent L-type calcium channel subunit alpha-1D-like [KO:K04853 ]
116692230 cacna1s; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857 ]
116706249 plcb1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858 ] [EC:3.1.4.11 ]
116670665 plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858 ] [EC:3.1.4.11 ]
116687305 inositol 1,4,5-trisphosphate receptor type 1-like isoform X1 [KO:K04958 ]
116687772 inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958 ]
116694480 itpr2; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959 ]
116673322 ppp1r12a; protein phosphatase 1 regulatory subunit 12A isoform X1 [KO:K06270 ]
116694165 protein phosphatase 1 regulatory subunit 12A-like isoform X1 [KO:K17457 ]
116705828 gna12; guanine nucleotide-binding protein subunit alpha-12 isoform X1 [KO:K04346 ]
116671786 guanine nucleotide-binding protein subunit alpha-13-like [KO:K04639 ]
116700073 rho guanine nucleotide exchange factor 12-like isoform X1 [KO:K07532 ]
116678893 arhgef12; rho guanine nucleotide exchange factor 12 isoform X1 [KO:K07532 ]
116691325 arhgef1; LOW QUALITY PROTEIN: rho guanine nucleotide exchange factor 1 [KO:K12330 ]
116707468 arhgef11; rho guanine nucleotide exchange factor 11 isoform X1 [KO:K12331 ]
116692455 rho-related GTP-binding protein RhoA-C-like isoform X1 [KO:K04513 ]
116673875 calcitonin gene-related peptide type 1 receptor-like isoform X1 [KO:K04577 ]
116687502 receptor activity-modifying protein 1-like isoform X1 [KO:K08447 ]
116703132 ramp2; receptor activity-modifying protein 2 isoform X1 [KO:K08448 ]
116693014 gnas; guanine nucleotide-binding protein G(s) subunit alpha [KO:K04632 ]
116688614 guanine nucleotide-binding protein G(s) subunit alpha-like [KO:K04632 ]
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
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