Roles of calcium, cyclic nucleotides, and protein kinase C in regulation of endothelial permeability.
We studied the effects of calcium, cyclic nucleotides, and protein kinase C on albumin transfer, electrical resistance, and cytoskeletal actin filaments in cultured human umbilical vein endothelial cells. The endothelial monolayer grown on collagen-treated filters markedly restricted the transfer of albumin relative to its transfer across the filter alone. Both Ca++ ionophore A23187 and ethyleneglycol tetraacetic acid disrupted the integrity of the endothelial monolayer, thereby increasing endothelial albumin transfer and decreasing electrical resistance in a concentration-dependent manner. Neither W-7, a calmodulin antagonist, nor TMB-8, an intracellular Ca++ antagonist, influenced endothelial permeability. In contrast, increases in intracellular cyclic adenosine 5'-monophosphate (AMP) and/or cyclic guanosine 5'-monophosphate (GMP) induced by dibutyryl cyclic AMP, forskolin, 3-isobutyl-1-methylxanthine, 8-bromo cyclic GMP, dibutyryl cyclic GMP, or sodium nitroprusside significantly elevated endothelial electrical resistance and inhibited albumin transfer; similar effects resulted from activation of protein kinase C by phorbol-12-myristate-13-acetate or 1-oleoyl-2-acetyl-glycerol. These substances ruffled the dense peripheral bands of F-actin without compromising the integrity of endothelial monolayer. These results suggest that calcium, cyclic nucleotides, and protein kinase C play important roles in the regulation of endothelial permeability and the maintenance of endothelial integrity.
First Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Y
Y
Yamada
T
T
Furumichi
H
H
Furui
T
T
Yokoi
T
T
Ito
K
K
Yamauchi
M
M
Yokota
H
H
Hayashi
H
H
Saito
D002118:Calcium / Q000502:physiology*; D002199:Capillary Permeability; D002478:Cells, Cultured; D004553:Electric Conductivity; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D008854:Microscopy, Electron; D008858:Microscopy, Phase-Contrast; D009712:Nucleotides, Cyclic / Q000502:physiology*; D011493:Protein Kinase C / Q000502:physiology*; D012709:Serum Albumin / Q000378:metabolism
D009712:Nucleotides, Cyclic; D012709:Serum Albumin; D011493:Protein Kinase C; D002118:Calcium