Atriopeptin inhibition of thrombin-mediated changes in the morphology and permeability of endothelial monolayers.
To determine the role of endothelial atriopeptin (AP) receptors, we examined the effect of AP-III on the morphology and macromolecular permeability of monolayer cultures of bovine aortic endothelial cells. AP-III alone (10(-9)-10(-6) M) had no observable effect on the morphology of the monolayers or their permeability to 125I-labeled albumin. However, incubation of the endothelial monolayers with AP-III (10(-8)-10(-6) M) antagonized thrombin-induced (1 unit/ml) cell-shape change and the formation of intercellular gaps. AP-III also opposed the effect of thrombin on the distribution of actin filaments in the endothelial cytoskeleton. Further, thrombin caused a 2-fold increase in monolayer permeability to 125I-labeled albumin, which was abolished by 10(-8)-10(-6) M AP-III pretreatment. Taken together with the findings that AP-III exhibited specific and saturable binding in these cells, these data suggest that AP regulates endothelial permeability through a receptor-mediated process.
Baron
D A
DA
Department of Cell and Molecular Pharmacology, Medical University of South Carolina, Charleston 29425.
Lofton
C E
CE
Newman
W H
WH
Currie
M G
MG
D000199:Actins / Q000378:metabolism; D000818:Animals; D001011:Aorta; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D002417:Cattle; D002463:Cell Membrane Permeability / Q000187:drug effects*; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D005456:Fluorescent Dyes; D007457:Iodine Radioisotopes; D008856:Microscopy, Fluorescence; D010590:Phalloidine; D012235:Rhodamines; D012710:Serum Albumin, Bovine / Q000378:metabolism; D013917:Thrombin / Q000494:pharmacology*
D000199:Actins; D005456:Fluorescent Dyes; D007457:Iodine Radioisotopes; D012235:Rhodamines; D010590:Phalloidine; D012710:Serum Albumin, Bovine; D009320:Atrial Natriuretic Factor; D013917:Thrombin