Entry |
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Name |
Vascular smooth muscle contraction - Loxodonta africana (African savanna elephant)
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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.
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Class |
Organismal Systems; Circulatory system
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Pathway map |
lav04270 | Vascular smooth muscle contraction |

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Other DBs |
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Organism |
Loxodonta africana (African savanna elephant) [GN: lav]
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Gene |
100656672 | GNAQ; guanine nucleotide-binding protein G(q) subunit alpha isoform X1 [KO:K04634] |
100656201 | KCNMA1; calcium-activated potassium channel subunit alpha-1 isoform X6 [KO:K04936] |
100675383 | KCNU1; LOW QUALITY PROTEIN: potassium channel subfamily U member 1 [KO:K05274] |
100663278 | KCNMB1; calcium-activated potassium channel subunit beta-1 [KO:K04937] |
100658510 | KCNMB2; calcium-activated potassium channel subunit beta-2 [KO:K04938] |
100657662 | KCNMB3; calcium-activated potassium channel subunit beta-3 isoform X3 [KO:K04939] |
100668504 | KCNMB4; calcium-activated potassium channel subunit beta-4 [KO:K04941] |
100659992 | CACNA1D; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851] |
100674649 | CACNA1F; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1F [KO:K04853] |
100673089 | CACNA1S; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857] |
100670617 | PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X3 [KO:K05858] [EC:3.1.4.11] |
100672435 | PLCB1; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11] |
100668575 | PLCB2; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11] |
100663829 | PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11] |
100665028 | ITPR1; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958] |
100659666 | ITPR3; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960] |
100659377 | PPP1R14A; protein phosphatase 1 regulatory subunit 14A [KO:K12328] |
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] |
100675940 | PPP1R12B; protein phosphatase 1 regulatory subunit 12B isoform X3 [KO:K12329] |
100669550 | PPP1R12C; LOW QUALITY PROTEIN: protein phosphatase 1 regulatory subunit 12C [KO:K17457] |
100676444 | GNA12; guanine nucleotide-binding protein subunit alpha-12 [KO:K04346] |
100664965 | GNA13; guanine nucleotide-binding protein subunit alpha-13 [KO:K04639] |
100661002 | ARHGEF12; rho guanine nucleotide exchange factor 12 isoform X1 [KO:K07532] |
100674589 | ARHGEF1; rho guanine nucleotide exchange factor 1 isoform X2 [KO:K12330] |
100673301 | ARHGEF11; rho guanine nucleotide exchange factor 11 isoform X1 [KO:K12331] |
100670968 | CALCRL; LOW QUALITY PROTEIN: calcitonin gene-related peptide type 1 receptor [KO:K04577] |
100655206 | guanine nucleotide-binding protein G(s) subunit alpha isoform X1 [KO:K04632] |
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Compound |
C01245 | D-myo-Inositol 1,4,5-trisphosphate |
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Reference |
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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 |
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Reference |
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Authors |
Ogut O, Brozovich FV |
Title |
Regulation of force in vascular smooth muscle. |
Journal |
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Reference |
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Authors |
Hilgers RH, Webb RC |
Title |
Molecular aspects of arterial smooth muscle contraction: focus on Rho. |
Journal |
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Reference |
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Authors |
Schlossmann J, Feil R, Hofmann F |
Title |
Signaling through NO and cGMP-dependent protein kinases. |
Journal |
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Reference |
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Authors |
Mehta PK, Griendling KK |
Title |
Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system. |
Journal |
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Reference |
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Authors |
Kim HR, Appel S, Vetterkind S, Gangopadhyay SS, Morgan KG |
Title |
Smooth muscle signalling pathways in health and disease. |
Journal |
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Reference |
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Authors |
Fukata Y, Amano M, Kaibuchi K |
Title |
Rho-Rho-kinase pathway in smooth muscle contraction and cytoskeletal reorganization of non-muscle cells. |
Journal |
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Reference |
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Authors |
Dimopoulos GJ, Semba S, Kitazawa K, Eto M, Kitazawa T |
Title |
Ca2+-dependent rapid Ca2+ sensitization of contraction in arterial smooth muscle. |
Journal |
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Reference |
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Authors |
Hynynen MM, Khalil RA |
Title |
The vascular endothelin system in hypertension--recent patents and discoveries. |
Journal |
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Reference |
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Authors |
Brain SD, Grant AD |
Title |
Vascular actions of calcitonin gene-related peptide and adrenomedullin. |
Journal |
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Reference |
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Authors |
Roman RJ |
Title |
P-450 metabolites of arachidonic acid in the control of cardiovascular function. |
Journal |
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Reference |
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Authors |
Surks HK |
Title |
cGMP-dependent protein kinase I and smooth muscle relaxation: a tale of two isoforms. |
Journal |
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Reference |
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Authors |
Vanhoutte PM |
Title |
Endothelium-dependent hyperpolarizations: the history. |
Journal |
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Reference |
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Authors |
Davis MJ, Hill MA |
Title |
Signaling mechanisms underlying the vascular myogenic response. |
Journal |
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Reference |
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Authors |
Fleming I. |
Title |
Cytochrome p450 and vascular homeostasis. |
Journal |
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Reference |
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Authors |
Carvajal JA, Germain AM, Huidobro-Toro JP, Weiner CP |
Title |
Molecular mechanism of cGMP-mediated smooth muscle relaxation. |
Journal |
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Reference |
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Authors |
Ko EA, Han J, Jung ID, Park WS |
Title |
Physiological roles of K+ channels in vascular smooth muscle cells. |
Journal |
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Reference |
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Authors |
Woodard GE, Rosado JA |
Title |
Natriuretic peptides in vascular physiology and pathology. |
Journal |
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Reference |
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Authors |
Berry C, Touyz R, Dominiczak AF, Webb RC, Johns DG |
Title |
Angiotensin receptors: signaling, vascular pathophysiology, and interactions with ceramide. |
Journal |
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Reference |
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Authors |
Hirano K, Hirano M, Kanaide H |
Title |
Regulation of myosin phosphorylation and myofilament Ca2+ sensitivity in vascular smooth muscle. |
Journal |
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Reference |
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Authors |
Freeman EJ, Ruehr ML, Dorman RV |
Title |
ANG II-induced translocation of cytosolic PLA2 to the nucleus in vascular smooth muscle cells. |
Journal |
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Reference |
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Authors |
Murphy TV, Spurrell BE, Hill MA |
Title |
Cellular signalling in arteriolar myogenic constriction: involvement of tyrosine phosphorylation pathways. |
Journal |
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Related pathway |
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KO pathway |
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LinkDB |
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