重组中性内肽酶EC.3.4.24.11对内皮素-1和大内皮素-1的代谢作用
Metabolism of endothelin-1 and big endothelin-1 by recombinant neutral endopeptidase EC.3.4.24.11.
作者信息
Abassi Z A, Golomb E, Bridenbaugh R, Keiser H R
机构信息
Hypertension-Endocrine Branch, National Heart, Lung & Blood Institute, National Institutes of Health, Bethesda, MD 20892.
出版信息
Br J Pharmacol. 1993 Aug;109(4):1024-8. doi: 10.1111/j.1476-5381.1993.tb13724.x.
Abstract
- Inhibitors of neutral endopeptidase EC.3.4.24.11 (NEP) have been shown to attenuate the hypertensive effect of big-endothelin-1 (BET-1) in rats. To determine whether NEP converts BET-1 to endothelin-1 (ET-1), the effect of a recombinant NEP (rNEP) on BET-1 and on ET-1 was assessed in vitro. 2. Incubation of [125I]-ET-1 with 1 microgram ml-1 of rNEP resulted in degradation of the peptide within minutes. Increase in the amount of rNEP to 10 micrograms ml-1 led to total cleavage of [125I]-ET-1 within seconds. 3. Phosphoramidon (10 microM) or SQ-28,603 (100 microM) totally suppressed the degradation of [125I]-ET-1 by rNEP. 4. The degradation of [125I]-BET-1 by either 1 or 10 micrograms ml-1 of rNEP was much slower than that of [125I]-ET-1. Again, both phosphoramidon and SQ 28,603 protected the peptide from degradation. 5. Intact [125I]-ET-1 was not observed when [125I]-BET-1 was incubated with rNEP. 6. These data show that neutral endopeptidase EC.3.4.24.11 is not an endothelin converting enzyme.
摘要
- 中性内肽酶EC.3.4.24.11（NEP）抑制剂已被证明可减弱大鼠体内大内皮素-1（BET-1）的升压作用。为了确定NEP是否将BET-1转化为内皮素-1（ET-1），在体外评估了重组NEP（rNEP）对BET-1和ET-1的作用。2. 将[125I]-ET-1与1微克/毫升的rNEP一起孵育，几分钟内肽就会降解。将rNEP的量增加到10微克/毫升，会在几秒钟内导致[125I]-ET-1完全裂解。3. 磷酰胺（10微摩尔）或SQ-28,603（100微摩尔）完全抑制了rNEP对[125I]-ET-1的降解。4. 1微克/毫升或10微克/毫升的rNEP对[125I]-BET-1的降解比[125I]-ET-1慢得多。同样，磷酰胺和SQ 28,603都保护该肽不被降解。5. 当[125I]-BET-1与rNEP一起孵育时，未观察到完整的[125I]-ET-1。6. 这些数据表明中性内肽酶EC.3.4.24.11不是内皮素转化酶。
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