OBJECTIVES: @entity556 induces endothelial barrier failure by activating the contractile machinery of endothelial cells. Contractile activation is due to an increase in @entity3097 ( @entity3097 ) phosphorylation. Here, it was investigated whether stimulation of endothelial cells with @entity855 can interrupt this @entity556 -induced pathomechanism. METHODS: In cultured @entity1 umbilical vein endothelial cells, cytosolic @entity460 [ @entity141 ](i) ( @entity593 method), phosphorylation of @entity3097 , isometric tension and permeability for albumin were studied. RESULTS: @entity556 (0.2 U/ml) increased [ @entity141 ](i) from a basal level of 78+/-8 to 570+/-63 nM (mean+/-S.D., n=5, P<0.05), @entity3097 phosphorylation from 71+/-7 to 163+/-18%, isometric tension from 157+/-17 to 232+/-26 microN, and permeability from 2.8+/-0.4 to 11.6+/-1 x 10(-6) cm/s. Co-presence of @entity855 (10 microM) and @entity556 did not alter the [ @entity141 ](i) rise, but reduced @entity3097 phosphorylation to 59.8+/-10%, isometric tension to 174+/-14 microN, and permeability to 5.4+/-0.6 x 10(-6) cm/s. The @entity556 -induced rise in @entity3097 phosphorylation was sensitive to reduction of [ @entity141 ](i) It was accompanied by an increase in Rho activation, and was inhibited by @entity12223 (10 microM), a Rho-kinase blocker. The @entity855 -induced decrease in @entity3097 phosphorylation was not sensitive to [ @entity141 ](i). It was not accompanied by changes in @entity3547 activation, and could not by suppressed by @entity12223 . CONCLUSIONS: @entity855 antagonizes the @entity141 - and Rho-dependent effects of @entity556 on @entity3097 phosphorylation most likely by a @entity141 - and Rho-independent activation of @entity3097 phosphatase. It thereby functionally antagonizes the @entity556 -induced increase in monolayer tension and permeability.

@entity855 antagonism of XXXX -induced endothelial barrier permeability.

@entity1 :: ('9606', 'Species') :: ['human'] @entity556 :: ('2147', 'Gene') :: ['Thrombin', 'thrombin'] @entity3547 :: ('387', 'Gene') :: ['RhoA'] @entity12223 :: ('MESH:C108830', 'Chemical') :: ['Y-27632'] @entity593 :: ('MESH:D016257', 'Chemical') :: ['Fura 2'] @entity3097 :: ('23209', 'Gene') :: ['MLC', 'myosin light chain'] @entity460 :: ('MESH:D002118', 'Chemical') :: ['calcium'] @entity141 :: ('CHEBI:29108', 'Chemical') :: ['Ca(2+)'] @entity855 :: ('MESH:D000255', 'Chemical') :: ['ATP']
@entity556 :: (2147,Gene) :: ['thrombin']
