Activation of endothelial cell kinin receptors leads to intracellular calcium increases and filamin translocation: regulation by protein kinase C.
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-Arg9-bradykinin cause filamin redistribution from the plasma membrane to the cytosol of confluent EC. Kinin-induced filamin translocation parallels the dynamics of intracellular Ca2+ increases. Pretreatment with kinin receptor antagonists blocks the Ca2+ response as well as filamin translocation induced by kinins. Protein kinase C activation prior to kinin stimulation attenuates intracellular Ca2+ increases and filamin translocation. BAPTA, a cell-permeable Ca2+ chelator, attenuates bradykinin-induced intracellular Ca2+ 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 Ca2+ increases. This Ca2+ signalling, which is downregulated by protein kinase C activation, is essential for kinin-induced filamin translocation.
Wang
Q
Q
Microvascular Research Laboratory, Boston University, MA 02215, USA.
Patton
W F
WF
Hechtman
H B
HB
Shepro
D
D
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D003285:Contractile Proteins / Q000378:metabolism*; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D004789:Enzyme Activation; D064448:Filamins; D007424:Intracellular Fluid; D007705:Kinins / Q000378:metabolism; D008840:Microfilament Proteins / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D018002:Receptors, Bradykinin / Q000378:metabolism*; D015398:Signal Transduction; D013347:Subcellular Fractions
D002614:Chelating Agents; D003285:Contractile Proteins; D064448:Filamins; D007705:Kinins; D008840:Microfilament Proteins; D018002:Receptors, Bradykinin; D004533:Egtazic Acid; D011493:Protein Kinase C; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium