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Biosynthesis and amino acid sequence and structure of endothelin-1, endothelin-2, and endothelin-3 and related sarafotoxins. ET-2 and ET-3 differ from ET-1 by two and five amino acids, respectively, while sarafotoxin differs by seven amino acids.
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Figure 1: Biosynthesis and amino acid sequence and structure of endothelin-1, endothelin-2, and endothelin-3 and related sarafotoxins. ET-2 and ET-3 differ from ET-1 by two and five amino acids, respectively, while sarafotoxin differs by seven amino acids.

Mentions: The endothelins are a family of 21 amino acid peptides, of which there are three distinct isoforms (ET-1, ET-2, and ET-3). The isoforms ET-2 and ET-3 differ from ET-1 by two and six amino acids, respectively, and share significant homology, especially at the carboxy terminus with sarafotoxins a-e (Fig. 1). Endothelin-1 is the most abundant isoform and has been best characterized. The lung has the highest levels of ET-1 secreted by endothelium, smooth muscle, airway epithelium, and a variety of other cells (Table 2). ET-1 also circulates in the plasma. In the normal lung, ET-1 mainly localizes to vascular endothelium, airway and vascular smooth muscle cells and, to a lesser degree, the epithelium. ET-2 has similar biologic functions as ET-1 and is found in the myocardium, kidney and placental tissues. ET-3 also circulates in plasma and is found in the central nervous system, gastrointestinal tract, lung, and kidney although the cellular source is not clear. The gene for ET-1 is located on chromosome 6, that for ET-2 on chromosome 1, and the gene for ET-3 on chromosome 20 [5].

Role of endothelin-1 in lung disease

Fagan KA, McMurtry IF, Rodman DM - Respir. Res. (2001)

Bottom Line: Endothelin-1 (ET-1) is a 21 amino acid peptide with diverse biological activity that has been implicated in numerous diseases.ET-1 is a potent mitogen regulator of smooth muscle tone, and inflammatory mediator that may play a key role in diseases of the airways, pulmonary circulation, and inflammatory lung diseases, both acute and chronic.This review will focus on the biology of ET-1 and its role in lung disease.

Affiliation: Cardiovascular Pulmonary Research Laboratory, Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA. karen.fagan@uchsc.edu

ABSTRACT
Endothelin-1 (ET-1) is a 21 amino acid peptide with diverse biological activity that has been implicated in numerous diseases. ET-1 is a potent mitogen regulator of smooth muscle tone, and inflammatory mediator that may play a key role in diseases of the airways, pulmonary circulation, and inflammatory lung diseases, both acute and chronic. This review will focus on the biology of ET-1 and its role in lung disease.

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