Phillips M I, Speakman E A, Kimura B
Department of Physiology, College of Medicine, Gainesville, FL 32610.
Regul Pept. 1993 Jan 22;43(1-2):1-20. doi: 10.1016/0167-0115(93)90403-u.
The cloning of renin, angiotensinogen and angiotensin converting enzyme genes have established a widespread presence of these components of the renin-angiotensin system in multiple tissues. New sites of gene expression and peptide products in different tissues has provided strong evidence for the production of angiotensin independently of the endocrine blood borne system. In addition, the cloning of the angiotensin receptor (AT1) gene has confirmed the widespread distribution of angiotensin and suggested new functions for the peptide. This review of various tissues shows the variation in gene expression between tissues and angiotensin levels, and the fragmentary state of our knowledge in this area. As yet we cannot state that the gene expression of the substrates, enzymes and peptide products are involved in a single cell synthesis. This is not so much evidence against a paracrine function for tissue angiotensin, as lack of detailed, accurate intracellular information. The low abundance of renin in brain, spleen, lung and thymus compared to kidney, adrenal, heart, testes, and submandibular gland may suggest that there are both tissue renin-angiotensin systems (RAS) and nonrenin-angiotensin systems (NRAS). The NRAS could function through cleavage of angiotensinogen by serine proteinases such as tonin and cathepsin G to form Ang II directly. Although much angiotensinogen is extracellular and could therefore be a site of synthesis outside of the cell, intracellular angiotensinogen in a NRAS process could produce Ang II intracellularly without requiring extracellular conversion of Ang I to Ang II by ACE. In summary, renin mRNA is found in high concentrations in kidney, adrenal and testes and decreasing lower concentrations in ovary, liver, brain, spleen, lung and thymus. Angiotensinogen mRNA is found in the following tissues in descending order of abundance: liver, fat cells, brain (glial cells), kidney, ovary, adrenal gland, heart, lung, large intestine and stomach. It is debatable whether angiotensinogen and renin mRNA are expressed in blood vessels. The evidence that is lacking for a paracrine function of angiotensin is a complete description of the intracellular molecular synthesis and release of Ang II from single cells of promising tissues. Such tissues, SMG, ovary, testes, adrenal, pituitary and brain (neurons and glia) are potent sources of RAS components for future studies. Although the evidence for a paracrine function of angiotensin II is incomplete, it is an important concept for progressing toward the understanding of tissue peptide physiology and the significance of their gene regulation.
肾素、血管紧张素原和血管紧张素转换酶基因的克隆已证实，肾素 - 血管紧张素系统的这些组分广泛存在于多种组织中。不同组织中基因表达新位点和肽产物的发现，为血管紧张素独立于内分泌血源系统的产生提供了有力证据。此外，血管紧张素受体（AT1）基因的克隆证实了血管紧张素的广泛分布，并提示了该肽的新功能。本文对各种组织的综述显示了组织间基因表达和血管紧张素水平的差异，以及我们在该领域知识的碎片化状态。目前我们尚不能确定底物、酶和肽产物的基因表达是否参与单细胞合成。这与其说是反对组织血管紧张素旁分泌功能的证据，不如说是缺乏详细、准确的细胞内信息。与肾脏、肾上腺、心脏、睾丸和下颌下腺相比，脑、脾、肺和胸腺中肾素含量较低，这可能表明存在组织肾素 - 血管紧张素系统（RAS）和非肾素 - 血管紧张素系统（NRAS）。NRAS可能通过丝氨酸蛋白酶（如胰蛋白酶和组织蛋白酶G）裂解血管紧张素原直接形成Ang II发挥作用。虽然许多血管紧张素原位于细胞外，因此可能是细胞外合成的位点，但NRAS过程中的细胞内血管紧张素原可在细胞内产生Ang II，而无需ACE将细胞外的Ang I转化为Ang II。总之，肾素mRNA在肾脏、肾上腺和睾丸中浓度较高，而在卵巢、肝脏、脑、脾、肺和胸腺中的浓度逐渐降低。血管紧张素原mRNA在以下组织中的丰度依次递减：肝脏、脂肪细胞、脑（神经胶质细胞）、肾脏、卵巢、肾上腺、心脏、肺、大肠和胃。血管紧张素原和肾素mRNA是否在血管中表达仍存在争议。血管紧张素旁分泌功能缺乏的证据是对有望进行研究的组织中单个细胞内Ang II的分子合成和释放的完整描述。这些组织，如下颌下腺、卵巢、睾丸、肾上腺、垂体和脑（神经元和神经胶质细胞）是未来研究RAS组分的重要来源。虽然血管紧张素II旁分泌功能的证据并不完整，但它是理解组织肽生理学及其基因调控意义的重要概念。
