ROLES OF CALCIUM, CYCLIC-NUCLEOTIDES, AND PROTEIN KINASE-C IN REGULATION OF ENDOTHELIAL PERMEABILITY

被引:71
作者
YAMADA, Y [1 ]
FURUMICHI, T [1 ]
FURUI, H [1 ]
YOKOI, T [1 ]
ITO, T [1 ]
YAMAUCHI, K [1 ]
YOKOTA, M [1 ]
HAYASHI, H [1 ]
SAITO, H [1 ]
机构
[1] NAGOYA UNIV,SCH MED,DEPT PATHOL,NAGOYA,AICHI 466,JAPAN
来源
ARTERIOSCLEROSIS | 1990年 / 10卷 / 03期
关键词
Albumin transfer; Calcium; Cyclic nucleotides; Electrical resistance; Endothelial cells; F-actin; Permeability; Protein kinase C;
D O I
10.1161/01.ATV.10.3.410
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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-B, 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.
引用
收藏
页码:410 / 420
页数:11
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