Proline in vasoactive peptides: consequences for peptide hydrolysis in the lung.
Proline in vasoactive peptides: consequences for peptide hydrolysis in the lung.
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血管活性肽中的脯氨酸：肺中肽水解的后果。
DOI：
10.1152/ajplung.1999.276.2.l341
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Dawson,CA
中科院分区：
文献类型：
--
作者：
Merker,MP;Audi,SH;Brantmeier,BM;Nithipatikom,K;Goldman,RS;Roerig,DL;Dawson,CA
要检查的假设，即transomers的缓激肽和[Gly 6]缓激肽优先水解肺肽酶，我们研究了这些肽在灌注的大鼠肺使用生物测定后，单次推注和肺再循环后的高效液相色谱法的部分失活。在生物测定研究中，当肽通过肺时，需要25.6倍以上的缓激肽或7倍以上的[Gly 6]缓激肽才能引起与肽不通过肺时产生的收缩相当的收缩。在再循环研究中，观察到具有快速和缓慢阶段的水解进展曲线，缓激肽在快速阶段水解的分数高于[Gly 6]缓激肽。亲环素增加了两种肽在缓慢阶段的水解速率。动力学分析表明，缓慢水解的肽部分，大概是cisfraction，缓激肽为0.13，[Gly 6]缓激肽为0.43，顺式-反式异构化速率常数分别为0.074和0.049 s-1，与已发表的核磁共振研究一致。
To examine the hypothesis thattransisomers of bradykinin and [Gly6]bradykinin are preferentially hydrolyzed by lung peptidases, we studied the fractional inactivation of these peptides in the perfused rat lung using a bioassay after a single-pass bolus injection and high-performance liquid chromatography after lung recirculation. In the bioassay studies, when the peptides passed through the lung, 25.6-fold more bradykinin or 7-fold more [Gly6]bradykinin was required to elicit a contraction equivalent to that produced when the peptides did not pass through the lung. In the recirculation studies, hydrolysis progress curves with rapid and slow phases were observed, with a higher fraction of bradykinin than [Gly6]bradykinin hydrolyzed in the rapid phase. Cyclophilin increased the hydrolysis rate during the slow phase for both peptides. Kinetic analysis indicated that the slowly hydrolyzed peptide fraction, presumably thecisfraction, was 0.13 for bradykinin and 0.43 for [Gly6]bradykinin withcis-transisomerization rate constants of 0.074 and 0.049 s−1, respectively, consistent with published nuclear magnetic resonance studies.