Warner T D
William Harvey Research Institute, St Bartholomew's Hospital Medical College, London, U.K.
Eur Heart J. 1993 Nov;14 Suppl I:42-7.
The endothelins are a family of three widely expressed 21 amino acid peptides. Apart from the ability to constrict vascular smooth muscle, they have numerous other potent effects, from enhancing mitogenesis to influencing nervous function. The pathway of their production involves the initial synthesis of a predominantly inactive 38 to 41 amino acid precursor, big endothelin, which is cleaved to the active form by an as yet unidentified, but widely distributed, endothelin-converting enzyme. This enzyme has been partially characterized and appears to be a metalloprotease, active at neutral pH, which is inhibited by phosphoramidon. However, other enzymes, including those contained in inflammatory cells, can also convert big endothelin to its active form. Research in the past 2 to 3 years has revealed at least two endothelin receptors. These are widely distributed throughout the body and are present, for instance, on vascular and non-vascular smooth muscle, nervous tissue, and endothelial and epithelial cells. There is also a fairly large degree of heterogeneity between species in the distribution of these endothelin receptors. The endothelins have been widely implicated in a number of disease states and the recent development of selective and non-selective antagonists of these receptors, such as BQ-123, PD 142893, and Ro 46-2005 is finally making available the tools required to elucidate their true roles.
内皮素是一族由三种广泛表达的含21个氨基酸的肽组成。除了具有收缩血管平滑肌的能力外，它们还有许多其他强效作用，从增强细胞有丝分裂到影响神经功能。其产生途径涉及最初合成一种主要无活性的含38至41个氨基酸的前体，即大内皮素，它被一种尚未明确但分布广泛的内皮素转换酶切割成活性形式。这种酶已得到部分表征，似乎是一种金属蛋白酶，在中性pH下有活性，可被磷酰胺素抑制。然而，其他酶，包括炎症细胞中所含的酶，也能将大内皮素转化为其活性形式。过去两到三年的研究已揭示至少两种内皮素受体。它们广泛分布于全身，例如存在于血管和非血管平滑肌、神经组织以及内皮细胞和上皮细胞上。这些内皮素受体在不同物种间的分布也存在相当大程度的异质性。内皮素已被广泛认为与多种疾病状态有关，最近这些受体的选择性和非选择性拮抗剂，如BQ - 123、PD 142893和Ro 46 - 2005的开发，终于提供了阐明其真正作用所需的工具。
