Chappell M C, Brosnihan K B, Diz D I, Ferrario C M
Department of Brain and Vascular Research, Cleveland Clinic Foundation, Ohio 44195-5070.
J Biol Chem. 1989 Oct 5;264(28):16518-23.
Tissue and plasma forms of angiotensin (Ang) peptides were characterized by reverse-phase high performance liquid chromatography and three specific radioimmunoassays. This method allowed resolution of 10 Ang peptides and revealed distinctive distributions for the three principal Ang peptides in the brain, adrenal gland, and plasma. In extracts from the rat hypothalamus, approximately equimolar amounts of Ang-(1-7), Ang-II, and Ang-I were detected (1.10, 1.18, and 1.45 pmol/g of tissue, respectively). A similar profile was observed in the medulla oblongata and amygdala, although the content of these three peptides was 40-70% less than that seen in the hypothalamus. In the adrenal gland, the predominant peptide was Ang-II (1.07 pmol/g); levels of Ang-(1-7) (0.19 pmol/g) and Ang-I (0.14 pmol/g) were approximately 20% that of Ang-II. In plasma, the major angiotensin was Ang-I (0.13 pmol/ml), with lower levels of Ang-(1-7) and Ang-II (0.01-0.02 pmol/ml). This study is the first demonstration of the endogenous presence of Ang-(1-7) in central and peripheral tissues of the rat. Moreover, the data suggest tissue-specific processing of angiotensins, with Ang-(1-7) being a predominant Ang peptide in the central nervous system. In light of the recent biological properties described for this peptide, Ang-(1-7) may represent an active member of Ang peptides in the brain.
通过反相高效液相色谱法和三种特异性放射免疫测定法对血管紧张素(Ang)肽的组织和血浆形式进行了表征。该方法可分离出10种Ang肽,并揭示了三种主要Ang肽在脑、肾上腺和血浆中的独特分布。在大鼠下丘脑提取物中,检测到了近似等摩尔量的Ang-(1-7)、Ang-II和Ang-I(分别为1.10、1.18和1.45 pmol/g组织)。在延髓和杏仁核中观察到了类似的分布情况,尽管这三种肽的含量比下丘脑低40%-70%。在肾上腺中,主要的肽是Ang-II(1.07 pmol/g);Ang-(1-7)(0.19 pmol/g)和Ang-I(0.14 pmol/g)的水平约为Ang-II的20%。在血浆中,主要的血管紧张素是Ang-I(0.13 pmol/ml),Ang-(1-7)和Ang-II的水平较低(0.01-0.02 pmol/ml)。本研究首次证明了大鼠中枢和外周组织中内源性存在Ang-(1-7)。此外,数据表明血管紧张素存在组织特异性加工,Ang-(1-7)是中枢神经系统中主要的Ang肽。鉴于最近描述的该肽的生物学特性,Ang-(1-7)可能代表脑中Ang肽的一个活性成员。