Regulation of Endothelial Barrier Function by the cAMP-Dependent Protein Kinase

摘要: Elevation of cAMP promotes the endothelial cell (EC) barrier and protects lung from edema development. Thus, we tested hypothesis that both increases decreases in PKA modulate EC function coordinate distribution regulatory, adherence, cytoskeletal proteins. Inhibition activity by RpcAMPS activation cholera toxin was verified assay kemptide phosphorylation digitonin permeabilized EC. or overexpression endogenous inhibitor, PKI, decreased monolayer electrical impedance exacerbated produced agonists (thrombin PMA). directly increased F-actin content organization into stress fibers, co-staining actin with phosphatase 2B myosin light chain kinase (MLCK), caused reorganization focal adhesions, catenin at borders. These findings are similar to those evoked thrombin. In contrast, prevented agonist-induced resistance decrease protein redistribution. Although attenuated thrombin-induced (MLC) phosphorylation, inhibition per se did not cause MLC affect [Ca2+]i. studies indicate a alone can produce disruption via mechanisms involving MLCK support central role for cAMP/PKA regulation adhesive which correlates altered function.