Structural analysis of digitalis-like substance for the promoter of essential hypertention

原发性高血压促进剂类洋地黄物质的结构分析

• 批准号: 07457618
• 负责人: ITOH Hajime
• 金额: $ 0.58万
• 依托单位: Kitasato University School of Allied Health Sciences
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07457618/
• 关键词: essential hypertention; the third factor; digitalis-like substance; Na^+, K^+-ATPase

A sepecific inhibitor of sodium-potassium-activatedadenosine 5'-triphosphatase (Na^+/K^+-ATPase) in urines from the patients with hyperpiesia was purified and the biochemical properties of the inhibitor was characterized. It was found that the inhibitor was directly purified from human urine with various HPLC systems including the column for sugar separation. The purified inhibitor was eluted as a single peak by ion-exchage chromatography in the sugar analytical system. The inhibitor in the peak fraction was thought to be an inducer of essential hypertension, because the time-dependent decrease of the specific peak was exactly correlated with its inhibitory activity. The inhibitory activity of the inhibitor was reduced in a time-dependent manner. Under the conditions, there were no detectable a specific peak of the inhibitor, but four peaks were observd when the compounds were generated from the inhibitor by spontaneous alteration.This analytical system revealed the existence of sugars and amino groups in the inhibitor. Only a peak of these four compounds didn't passed through an amino-trap column. These results suggest that the Na^+/K^+-ATPase inhibitor has a sugar chain consisted of at least three sugars including amino groups, which may be responsible for the recognition of the specific receptor for Na^+/K^+-ATPase on the membrane of both smooth musle and adrenal basal cells.

提纯了高血压患者尿液中钠钾激活的腺苷5‘-三磷酸酶(Na~+/K~+-ATPase)的特异性抑制剂，并对其生化性质进行了表征。用包括糖分离柱在内的各种高效液相系统直接从人尿液中纯化了该抑制剂。在糖分析系统中，离子交换层析将纯化后的缓蚀剂洗脱为单峰。峰部分中的抑制物被认为是高血压的诱导物，因为特定峰随时间的减少与其抑制活性完全相关。该抑制剂的抑制活性呈时间依赖性降低。在此条件下，没有检测到缓蚀剂的特异峰，但当缓蚀剂自发变化生成化合物时，观察到四个峰，这一分析系统揭示了缓蚀剂中糖和氨基的存在。这四个化合物中只有一个峰没有通过氨基捕捉柱。这些结果表明，Na+/K+-ATPase抑制剂具有至少由3个糖基组成的糖链，这可能与平滑肌和肾上腺基底细胞膜上Na+/K+-ATPase特异性受体的识别有关。