HISTAMINE AND THROMBIN MODULATE ENDOTHELIAL FOCAL ADHESION THROUGH CENTRIPETAL AND CENTRIFUGAL FORCES

We examined the contribution of actin-myosin contraction to the modula tion of human umbilical vein endothelial cell focal adhesion caused by histamine and thrombin. Focal adhesion was measured as the electrical resistance across a cultured monolayer grown on a microelectrode. Act in-myosin contraction was measured as isometric tension of cultured mo nolayers grown on a collagen gel. Histamine immediately decreased elec trical resistance but returned to basal levels within 3-5 min. Histami ne did not increase isometric tension. Thrombin also immediately decre ased electrical resistance, but, however, resistance did not return to basal levels for 40-60 min. Thrombin also increased isometric tension . ML-7, an inhibitor of myosin light chain kinase, prevented increases in myosin light chain phosphorylation and increases in tension develo pment in cells exposed to thrombin. ML-7 did not prevent a decline in electrical resistance in cells exposed to thrombin. instead, ML-7 rest ored the electrical resistance to basal levels in a shorter period of time (20 min) than cells exposed to thrombin alone. Also. histamine su bsequently increased electrical resistance to above basal levels. and thrombin initiated an increase in resistance during the time of peak t ension development. Hence, histamine and thrombin modulate endothelial cell focal adhesion through centripetal and centrifugal forces.