1995
DOI: 10.1002/jcp.1041630311
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Abstract: Endothelial cell (EC) contraction results in intercellular gap formation and loss of the selective vascular barrier to circulating macromolecules. We tested the hypothesis that phosphorylation of regulatory myosin light chains (MLC) by Ca2+/calmodulin-dependent myosin light chain kinase (MLCK) is critical to EC barrier dysfunction elicited by thrombin. Thrombin stimulated a rapid (< 15 sec) increase in [Ca2+]i which preceded maximal MLC phosphorylation (60 sec) with a 6 to 8-fold increase above constitutive le… Show more

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Cited by 521 publications
(480 citation statements)
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“…Effect of Elevated cAMP on Agonist-induced Isometric Tension and Myosin RLC Phosphorylation-To test the hypothesis that cAMP-mediated decreases in myosin RLC phosphorylation are the result of inhibition of MLCK activity, BPAE monolayers were pretreated with Fsk/ IBMX and then stimulated with thrombin, an agonist that has been shown to activate MLCK in endothelial cells (1,40). Fig.…”
Section: Resultsmentioning
confidence: 99%
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“…Effect of Elevated cAMP on Agonist-induced Isometric Tension and Myosin RLC Phosphorylation-To test the hypothesis that cAMP-mediated decreases in myosin RLC phosphorylation are the result of inhibition of MLCK activity, BPAE monolayers were pretreated with Fsk/ IBMX and then stimulated with thrombin, an agonist that has been shown to activate MLCK in endothelial cells (1,40). Fig.…”
Section: Resultsmentioning
confidence: 99%
“…The primary pathway implicated in preventing increases in permeability is believed to occur through the activation of adenylate cyclase, accumulation of intracellular cAMP, and activation of PKA. 2 Even though there are numerous reports (1)(2)(3)(4)(5) implicating cAMP/PKA in enhancing barrier function and inhibiting endothelial cell contraction, the mechanism by which cAMP/PKA protects vascular integrity is poorly understood.…”
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confidence: 99%
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“…ROCK can phosphorylate the myosin light chain phosphatase targeting subunit (MYPT‐1), leading to inactivation of myosin light chain phosphatase, and accumulation of myosin light chain phosphorylated on Thr‐18 and Ser‐19 by myosin light chain kinase 11, 12. Several reports have suggested that inflammatory mediators promote excess phosphorylated myosin light chain, which may interact with actin to open intercellular junctions, either through contractile or retractile mechanisms 3, 13, 14, 15, 16, 17, 18. Despite these advances, a caveat to using inhibition of RhoA/ROCK to reduce microvascular hyperpermeability is the fact that this pathway is also important for maintaining endothelial barrier function under noninflammatory conditions,17, 19, 20 as RhoA activation near cell borders promotes endothelial barrier integrity 21.…”
Section: Introductionmentioning
confidence: 99%
“…EC contractile state is a key determinant of vascular permeability to ions and macromolecules. Exposure of human umbilical vein ECs (HUVECs) to thrombin and histamine results in rapid contraction, 14,15 which is secondary to the rearrangement of actin and myosin into stress fibers. 16 Like secretion, the contractile response is dependent on a rise in [Ca 2ĎŠ ] i and calmodulin.…”
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confidence: 99%