ACTIVATION OF ENDOTHELIAL-CELL KININ RECEPTORS LEADS TO INTRACELLULARCALCIUM INCREASES AND FILAMIN TRANSLOCATION - REGULATION BY PROTEIN-KINASE-C

Membrane-associated cytoskeletal proteins provide support for endothel ial cell (EC) junctional cell adhesion molecules. Nonmuscle filamin is a dimeric actin cross-linking protein that interacts with F-actin and membrane glycoproteins. Both bradykinin and des-Arg(9)-bradykinin cau se filamin redistribution from the plasma membrane to the cytosol of c onfluent EC. Kinin-induced filamin translocation parallels the dynamic s of intracellular Ca2+ increases. Pretreatment with kinin receptor an tagonists blocks the Ca2+ response as well as filamin translocation in duced by kinins. Protein kinase C activation prior to kinin stimulatio n attenuates intra cellular Ca2+ increases and filamin translocation. BAPTA, a cell-permeable Ca2+ chelator, attenuates bradykinin-induced i ntracellular Ca2+ increases and filamin translocation. This study demo nstrates that bovine pulmonary artery ECs express both kinin B1 and B2 receptors, and that activation of either receptor leads to intracellu lar Ca2+ increases. This Ca2+ signalling, which is downregulated by pr otein kinase C activation, is essential for kinin-induced filamin tran slocation. (C) 1997 Elsevier Science Inc.