Metabolism of vasoactive peptides by human endothelial cells in culture. Angiotensin I converting enzyme (kininase II) and angiotensinase.
Metabolism of vasoactive peptides by human endothelial cells in culture. Angiotensin I converting enzyme (kininase II) and angiotensinase.
复制标题
培养物中人内皮细胞对血管活性肽的代谢。
DOI：
--
复制
发表时间：
1977
影响因子：
15.9
通讯作者：
E. G. Erdös
中科院分区：
文献类型：
--
作者：
A. Johnson;E. G. Erdös
培养的内皮细胞为研究血管活性多肽与内皮的相互作用提供了模型。培养的人脐静脉内皮细胞具有血管紧张素转换酶(激动素II)和血管紧张素酶活性。当将这些多肽加入无蛋白培养瓶中时，完整的细胞单层既能激活血管紧张素I，又能灭活缓激肽。完整的悬浮细胞或裂解细胞将血管紧张素I转化为血管紧张素II，使缓激肽失活，并将马尿基二甘氨酸水解为马尿酸和二甘氨酸。这些作用可被转换酶的特异性抑制剂SQ 20881抑制。抗人肺转换酶抗体可部分抑制内皮细胞激氨酶活性。内皮细胞也可以灭活更长的缓激肽类似物，如卡利丁、蛋氨酰赖氨基缓激肽和缓激肽与500,000摩尔质量的葡聚糖共价偶联。经过连续四次传代培养，内皮细胞仍保持转换酶活性，表明该酶是由细胞表面合成的，显然是内皮细胞的标志，因为培养的人成纤维细胞、平滑肌细胞和幼年仓鼠肾细胞不含该酶。血管内皮细胞还含有一种氨基肽酶，它能同时分解血管紧张素II和合成底物--α-L-天冬氨酸β-萘胺。当细胞裂解时，血管紧张素酶活性升高，表明该酶定位于细胞内，α-L-天冬氨酸β-萘胺和血管紧张素Ⅱ的水解酶均被奥米克隆-菲咯啉抑制，表明该酶是一种A型八角氨酸酶。
Cultured endothelial cells provide a model for the study of interactions of vasoactive peptides with endothelium. Endothelial cell cultured from veins of human umbilical cords contain both angiotensin I converting enzyme (kininase II) and angiotensinase activities. Intact monolayers of cells can both activate angiotensin I and inactivate bradykinin when the peptides are added to culture flasks in protein-free medium. Intact suspended cells or lysed cells convert angiotensin I to angiotensin II, inactivate bradykinin, and hydrolyze hippuryldiglycine to hippuric acid and diglycine. These actions are inhibited by SQ 20881, the specific inhibitor of converting enzyme. The kininase activity of endothelial cells was partially inhibited by antibody to human lung converting enzyme. Endothelial cells also inactivate longer analogs of bradykinin, such as kallidin, methionyl-lysyl bradykinin, and bradykinin coupled covalently to 500,000 mol wt dextran. The endothelial cells retained converting enzyme activity through four successive subcultures, indicating that the enzyme is synthesized by the cells surface, and it is apparently a marker for endothelial cells, since cultured human fibroblasts, smooth muscle cells, and baby hamster kidney cells do not have it. Endothelial cells also contain an aminopheptidase which hydrolyzes both angiotensin II and the synthetic substrate, alpha-L-aspartyl beta-naphthylamide. The angiotensinase activity increased when the cells were lysed, which suggests that the enzyme is localized within the cells, Hydrolysis of both alpha-L-aspartyl beta-naphthylamide and angiotensin II was inhibited by omicron-phenanthroline, indicating that the enzyme is an A-tipe anigotensinase.