A human platelet angiotensin I-processing system. Identification of components and inhibition of angiotensin-converting enzyme by product.
A human platelet angiotensin I-processing system. Identification of components and inhibition of angiotensin-converting enzyme by product.
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DOI：
10.1016/s0021-9258(17)39531-5
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发表时间：
1985-07
期刊：
影响因子：
--
通讯作者：
R. A. Snyder;K. Watt;B. Wintroub
中科院分区：
文献类型：
--
作者：
R. A. Snyder;K. Watt;B. Wintroub
控制血管组织局部产生血管紧张素II的机制还不完全清楚。检测人血小板代谢血管紧张素I的能力。通过高效液相色谱法检测血小板依赖性血管紧张素I代谢，该方法可定量所用的血管紧张素I底物和形成的产物。血小板依赖性血管紧张素I代谢的主要产物被鉴定为des-Leu 10-血管紧张素I。血小板脱亮氨酸10-血管紧张素I生成活性的最适pH值为6.0-6.5，汞水杨酸（10（-4）M）可抑制100%，亮抑肽素（10（-4）M）可抑制86%，碘乙酰胺（10（-2）M）可抑制95%。通过Sephacryl S-200凝胶过滤测定，活性具有约Mr = 70，000。用钙离子载体（1-10 μ M）刺激的完整人血小板释放13.7-30.8%的des-Leu 10-血管紧张素I生成活性。血小板血管紧张素I代谢的主要产物Des-Leu 10-血管紧张素I抑制人血清和纯化的兔肺血管紧张素转换酶，I 50分别为3.7 × 10（-6）和2.0 × 10（-6）M。这些结果表明，血小板可能通过代谢前体肽血管紧张素I和生成内源性血管紧张素转换酶抑制剂des-Leu 10-血管紧张素I来控制血管部位局部血管紧张素II的形成。这种血小板依赖性途径可能有助于控制血管活性肽（如缓激肽和血管紧张素II）的局部水平，从而改变局部组织血流。
Mechanisms controlling the local generation of angiotensin II by vascular tissue are incompletely understood. Human platelets were examined for their ability to metabolize angiotensin I. Platelet-dependent angiotensin I metabolism was detected by a high performance liquid chromatography assay which allowed quantitation of angiotensin I substrate utilized and products formed. The major product of platelet-dependent angiotensin I metabolism was identified as des-Leu10-angiotensin I. The platelet des-Leu10-angiotensin I-generating activity had a pH optimum of 6.0-6.5 and was inhibited 100% by mersalyl acid (10(-4) M), 86% by leupeptin (10(-4) M), and 95% by iodoacetamide (10(-2) M). The activity had an approximate Mr = 70,000 as determined by Sephacryl S-200 gel filtration. Intact human platelets stimulated with calcium ionophore (1-10 microM) released 13.7-30.8% of the des-Leu10-angiotensin I-generating activity. Des-Leu10-angiotensin I, the major product of platelet angiotensin I metabolism, inhibited human serum and purified rabbit lung angiotensin-converting enzymes with an I50 of 3.7 X 10(-6) and 2.0 X 10(-6) M, respectively. These results suggest that the platelet may control local angiotensin II formation at vascular sites both by metabolism of the precursor peptide angiotensin I and by generation of an endogenous angiotensin-converting enzyme inhibitor, des-Leu10-angiotensin I. This platelet-dependent pathway may contribute to the control of local levels of vasoactive peptides, such as bradykinin and angiotensin II, so as to alter local tissue blood flow.