Entry
Name
Vascular smooth muscle contraction - Podarcis raffonei (Aeolian wall lizard)
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
Ortholog table
Other DBs
Organism
Podarcis raffonei (Aeolian wall lizard) [GN:
praf ]
Gene
128423785 guanine nucleotide-binding protein G(q) subunit alpha isoform X1 [KO:K04634 ]
128405531 GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635 ]
128413725 KCNMA1; calcium-activated potassium channel subunit alpha-1 isoform X1 [KO:K04936 ]
128407757 KCNMB1; calcium-activated potassium channel subunit beta-1 [KO:K04937 ]
128414786 KCNMB2; calcium-activated potassium channel subunit beta-2 isoform X1 [KO:K04938 ]
128422223 KCNMB4; calcium-activated potassium channel subunit beta-4 [KO:K04941 ]
128422166 CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850 ]
128408307 CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851 ]
128404904 CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853 ]
128415973 CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857 ]
128416343 MYL9; myosin regulatory light polypeptide 9 isoform X1 [KO:K12755 ]
128403455 PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858 ] [EC:3.1.4.11 ]
128410022 PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858 ] [EC:3.1.4.11 ]
128410023 PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858 ] [EC:3.1.4.11 ]
128408441 ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958 ]
128421863 ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959 ]
128416015 ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960 ]
128418182 PPP1R14A; protein phosphatase 1 regulatory subunit 14A [KO:K12328 ]
128419966 PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit isoform X1 [KO:K06269 ] [EC:3.1.3.16 ]
128411028 PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit isoform X1 [KO:K06269 ] [EC:3.1.3.16 ]
128422625 PPP1R12A; protein phosphatase 1 regulatory subunit 12A isoform X1 [KO:K06270 ]
128416233 PPP1R12B; protein phosphatase 1 regulatory subunit 12B isoform X1 [KO:K12329 ]
128400032 PPP1R12C; protein phosphatase 1 regulatory subunit 12C isoform X1 [KO:K17457 ]
128401334 GNA12; guanine nucleotide-binding protein subunit alpha-12 isoform X1 [KO:K04346 ]
128407252 GNA13; guanine nucleotide-binding protein subunit alpha-13 [KO:K04639 ]
128402896 ARHGEF12; rho guanine nucleotide exchange factor 12 isoform X1 [KO:K07532 ]
128418329 ARHGEF1; rho guanine nucleotide exchange factor 1 isoform X1 [KO:K12330 ]
128403433 ARHGEF11; rho guanine nucleotide exchange factor 11 isoform X1 [KO:K12331 ]
128398776 CALCRL; calcitonin gene-related peptide type 1 receptor [KO:K04577 ]
128415153 RAMP3; receptor activity-modifying protein 3 isoform X1 [KO:K08449 ]
128416513 GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoform X1 [KO:K04632 ]
128415221 IRAG1; inositol 1,4,5-triphosphate receptor associated 1 isoform X1 [KO:K12337 ]
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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