Kuwasako K, Kitamura K, Ishiyama Y, Washimine H, Kato J, Kangawa K, Eto T
First Department of Internal Medicine, Miyazaki Medical College, Kiyotake, Japan.
FEBS Lett. 1997 Sep 1;414(1):105-10. doi: 10.1016/s0014-5793(97)00971-x.
Proadrenomedullin N-terminal 20 peptide (PAMP-20) is a potent hypotensive peptide processed from the adrenomedullin (AM) precursor. We developed a specific radioimmunoassay which recognizes the C-terminal region of PAMP-20. Using this radioimmunoassay, the distribution of immunoreactive (ir-) PAMP was determined in porcine tissues. High concentrations of ir-PAMP were observed in the adrenal medulla and in the atrium, and these values were comparable to the corresponding concentrations of ir-AM. The concentration of ir-PAMP was almost the same as that of ir-AM in the kidney, while ir-PAMP was significantly lower than ir-AM in the ventricle, lung, and aorta. Reversed-phase high performance liquid chromatography in each porcine tissue sample revealed that two major peaks of ir-PAMP existed: one emerged at a position identical to that of authentic porcine PAMP-20; the other unknown peak was eluted earlier. The unknown peptide was purified to homogeneity from porcine adrenal medulla, and its complete amino acid sequence was determined. This peptide was found to be PAMP[9-20] with a C-terminal amide structure, and was named PAMP-12. Intravenous injections of PAMP-12 in anesthetized rats showed a significant hypotensive effect in a dose-dependent fashion, and the effect was comparable to that of PAMP-20. These data indicate that PAMP-12, a major component of ir-PAMP, is processed from the AM precursor, as is PAMP-20, and may participate in cardiovascular control.
前肾上腺髓质素N端20肽（PAMP - 20）是一种由肾上腺髓质素（AM）前体加工而成的强效降压肽。我们开发了一种特异性放射免疫分析法，可识别PAMP - 20的C端区域。利用这种放射免疫分析法，测定了猪组织中免疫反应性（ir -）PAMP的分布。在肾上腺髓质和心房中观察到高浓度的ir - PAMP，这些值与相应的ir - AM浓度相当。在肾脏中，ir - PAMP的浓度与ir - AM几乎相同，而在心室、肺和主动脉中，ir - PAMP明显低于ir - AM。对每个猪组织样品进行反相高效液相色谱分析显示，存在两个主要的ir - PAMP峰：一个出现在与 authentic猪PAMP - 20相同的位置；另一个未知峰洗脱较早。从猪肾上腺髓质中纯化该未知肽至同质，并确定其完整的氨基酸序列。发现该肽为具有C端酰胺结构的PAMP[9 - 20]，并命名为PAMP - 12。在麻醉大鼠中静脉注射PAMP - 12呈现出剂量依赖性的显著降压作用，且该作用与PAMP - 20相当。这些数据表明，ir - PAMP的主要成分PAMP - 12与PAMP - 20一样，是由AM前体加工而成的，可能参与心血管控制。
