METABOLISM OF VASOACTIVE PEPTIDES BY VASCULAR ENDOTHELIUM AND SMOOTH-MUSCLE AMINOPEPTIDASE-M
METABOLISM OF VASOACTIVE PEPTIDES BY VASCULAR ENDOTHELIUM AND SMOOTH-MUSCLE AMINOPEPTIDASE-M
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DOI：
10.1016/0006-2952(89)90165-2
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发表时间：
1989-01-01
影响因子：
5.8
通讯作者：
WARD, PE
中科院分区：
文献类型：
--
作者：
PALMIERI, FE;BAUSBACK, HH;WARD, PE
在培养的猪主动脉内皮细胞和平滑肌细胞中检测血管质膜氨肽酶M（AmM; EC 3.4.11.2）的细胞定位。AmM在平滑肌上高14倍（117 ± 0.01）。16单位/mg）比内皮细胞（8.4 . ±. 0.2）。与其细胞分布成比例，AmM水解胰激肽的N-末端产生缓激肽，并降解des（Asp 1）血管紧张素I、血管紧张素III、hepta（5-11）P物质和Met 5-脑啡肽。与此相反，缓激肽，血管紧张素II和P物质是耐AMM介导的水解。肽代谢在pH7.0时最佳，并被邻菲咯啉、bestatin抑制（Ki = 2.2 ± 0.1）。0.1μ M）和抑氨酶抑制剂（Ki = 25 ± 0.5 μ M）。5nM）。Des（Asp 1）血管紧张素I和血管紧张素III对AmM具有最高的亲和力（最低Km）（Km = 2.2 ± 0.5）。0.5和2.0 .+-。0.4接着是七（5-11）物质P（53.9 ± 0.5 μ M）。1.7μ M）和Met 5-脑啡肽（75.7 ±. 3.5μ M）。相比之下，Met 5-脑啡肽的最大水解速度更高（313 ± 1.5%）。2nmol/min/mg）比七（5-11）P物质（109 . ±. 18 nmol/min/mg）或血管紧张素III（26.5 ±. 1.0 nmol/min/mg）。正如对普通酶水解所预期的那样，AmM介导的脑啡肽降解被血管紧张素III竞争性抑制（Ki = 0.34 ± 0.05）。0.05μ M）、七（5-11）P物质（43.7 ±. 6.3μ M）和胰激肽（62 μ M）。这些数据表明，血管AmM可以调节血管活性肽在体内的水平，特别是在内皮细胞和平滑肌细胞表面受体的微环境。
The cellular localization of vascular plasma membrane aminopeptidase M (AmM; EC 3.4.11.2) was examined in cultured porcine aorta endothelium and smooth muscle cells. AmM was 14-fold higher on smooth muscle (117 .+-. 16 units/mg) than on endothelium (8.4 .+-. 0.2). Proportional to its cellular distribution, AmM hydrolyzed the N-terminus of kallidin to produce bradykinin, and degraded des(Asp1)angiotensin I, angiotensin III, hepta(5-11)substance P and Met5-enkephalin. In contrast, bradykinin, angiotensin II and substance P were resistant to AmM-mediated hydrolysis. Peptide metabolism was optimal at pH 7.0 and was inhibited by o-phenanthroline, bestatin (Ki = 2.2 .+-. 0.1 .mu.M) and amastatin (Ki = 25 .+-. 5 nM). Des(Asp1)angiotensin I and angiotensin III had the highest affinity (lowest Km) for AmM (Km = 2.2 .+-. 0.5 and 2.0 .+-. 0.4 .mu.M respectively), followed by hepta(5-11)substance P (53.9 .+-. 1.7 .mu.M) and Met5-enkephalin (75.7 .+-. 3.5 .mu.M). In contrast, maximal velocities of hydrolysis were higher for Met5-enkephalin (313 .+-. 2 nmol/min/mg) than for hepta(5-11)substance P (109 .+-. 18 nmol/min/mg) or angiotensin III (26.5 .+-. 1.0 nmol/min/mg). As expected for hydrolysis by a common enzyme, AmM-mediated enkephalin degradation was inhibited competitively by angiotensin III (Ki = 0.34 .+-. 0.05 .mu.M), hepta(5-11)substance P (43.7 .+-. 6.3 .mu.M) and kallidin (62 .mu.M). These data suggest that vascular AmM may modulate vasoactive peptide levels in vivo, particularly within the microenvironment of endothelial and smooth muscle cell surface receptors.