Activation of Endothelial Cell Kinin Receptors Leads to Intracellular Calcium Increases and Filamin Translocation: Regulation by Protein Kinase C

Abstract

Membrane-associated cytoskeletal proteins provide support for endothelial 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 cause filamin redistribution from the plasma membrane to the cytosol of confluent EC. Kinin-induced filamin translocation parallels the dynamics of intracellular Ca 2+ increases. Pretreatment with kinin receptor antagonists blocks the Ca 2+ response as well as filamin translocation induced by kinins. Protein kinase C activation prior to kinin stimulation attenuates intracellular Ca 2+ increases and filamin translocation. BAPTA, a cell-permeable Ca 2+ chelator, attenuates bradykinin-induced intracellular Ca 2+ increases and filamin translocation. This study demonstrates that bovine pulmonary artery ECs express both kinin B1 and B2 receptors, and that activation of either receptor leads to intracellular Ca 2+ increases. This Ca 2+ signalling, which is downregulated by protein kinase C activation, is essential for kinin-induced filamin translocation.