Role of converting enzyme in the responses of rabbit atria, aortas, and adrenal zona glomerulosa to [des-Asp1]angiotensin I.
Role of converting enzyme in the responses of rabbit atria, aortas, and adrenal zona glomerulosa to [des-Asp1]angiotensin I.
复制标题
转化酶在兔心房、主动脉和肾上腺肾小球带对 [des-Asp1] 血管紧张素 I 反应中的作用。
DOI：
10.1161/01.res.41.2.231
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发表时间：
1977
影响因子：
20.1
通讯作者：
M. Peach
中科院分区：
文献类型：
--
作者：
J. Ackerly;B. Tsai;M. Peach
研究了血管紧张素I （A I）和[des- asp ' b|血管紧张素I （des'-A I）分别在兔主动脉带、左心房、肾上腺带肾小球细胞悬液中转化为血管紧张素II （A II）和血管紧张素III （A III）。通过测量肽诱导的主动脉和心房张力发展的变化以及细胞悬液中甾体生成的变化，在存在和不存在Bothrops jararaca非肽转化酶抑制剂（CEI）的情况下，估计了A I和[des'-A I]的转化。研究了该酶制剂对组氨酸-亮氨酸的酶解作用。与A II相比，血管紧张素I和des -A I分别具有23%和1%的收缩活性（主动脉）和34%和4%的正性肌力活性（心房）。主动脉和心房转换酶的抑制减弱了对A I和des'-A I的反应，但没有显著改变对AH和A HI的反应。肾上腺细胞中AI和des'-A - I的类固醇生成活性依赖于转化，因为CEI处理特异性地消除了AI和des'-A - I诱导的醛固酮生物合成，而不改变aii或aiii的活性。肺酶测定AI和des’AI的Km值分别为80 /IM和30 /IM。A I和des'-A I的水解被CEI、A II和A HI竞争性地抑制。血管紧张素III是A I的几种代谢物中最有效的CEI，这些结果表明des'-A I是比A I更好的分离肺转化酶底物。本研究清楚地表明，纯化酶和组织转化酶可以快速转化des' a - I。这些数据与假设的从des'-A I到A I的n端降解形成A HI的替代途径是一致的。
SUMMARY Conversion of angiotensin I (A I) and [des-Asp' |angiotensin I (des'-A I) to angiotensin II (A II) and angiotensin III (A III), respectively, was studied in aortic strips, left atria, adrenal zone glomerulosa cell suspensions from rabbits, and with purified rabbit lung converting enzyme. Conversion of A I and [des'-A I] was estimated in the presence and absence of Bothrops jararaca nonapeptide, converting enzyme inhibitor (CEI), by measuring the changes in peptide-induced tension development in aortas and atria and on steroidogenesis in cell suspensions. The liberation of histidyl-leucine from AI and des'-A I by the enzyme preparation was studied. Angiotensin I and des'-A I possessed 23% and 1% contractile activity (aorta), and 34% and 4% positive inotropic activity (atria), respectively, when compared to A II. Inhibition of aortic and atrial converting enzymes attenuated responses to A I and des'-A I without significantly altering responses to AH and A HI. The steroidogenic activity of AI and des'-A I in adrenal cells was dependent on conversion since treatment with CEI specifically abolished aldosterone biosynthesis induced by AI and des'-A I without changing the activities of A II or A III. The Km values for AI and des'-A I determined with lung enzyme were 80 /IM and 30 /IM, respectively. The hydrolysis of A I and des'-A I was competitively inhibited by CEI, A II, and A HI. Angiotensin III was the most potent CEI among several metabolites of A I. These results indicate that des'-A I was a better substrate than A I for isolated pulmonary converting enzyme. The present investigation clearly indicates that des'-A I is rapidly converted by purified and tissue converting enzymes. The data are consistent with the postulated alternative pathway for formation of A HI from des'-A I subsequent to N-terminal degradation of A I.