Endothelin

  • OMIM: 131241
  • UniProt: P20800
  • OMIM: 131242
  • UniProt: P14138

Endothelins are peptide hormones in vertebrates, which are mainly produced by the endothelium of blood vessels. Endothelins are the most potent known vasoconstrictor substances, but they also act in the central nervous system. Mutations in the gene coding for endothelin-3 gene EDN3 can cause rare hereditary congenital megacolon, Undine 's syndrome and Waardenburg syndrome.

Paralogs

There are at least three known human paralogous variants of endothelin, which all have the same number of 21 amino acids. From them to endothelin -1 ( ET-1) is characterized by a particularly potent effect in the cardiovascular system. In addition, the paralogs endothelin-2 (ET -2) and endothelin-3 (ET -3) are formed. While it is known about the function of preferentially formed in the kidney, endothelin-2 bit could be detected for endothelin-3 In addition, a significance in the central nervous system (CNS). Of ET- 3, two isoforms are known.

In addition, a number of structurally similar substances from snake venoms are known ( so-called Sarafotoxine ) that have a Endothelinwirkung.

Function

When blood vessel changing ( vasoactive substance) it is a component of the body's system for regulating blood pressure and highly effective vasoconstrictor. Its vasoconstrictive and thus blutdrucksteigendernde effect is one hundred times as high as that of noradrenaline. It was initially assumed that it would only in the endothelium, the inner wall of the blood vessels of the entire body lining cell layer formed. In fact, many cells in the formation and release of endothelin in the situation.

Particularly in diseases of the coronary vessels, heart failure and atherosclerosis, increased endothelin is frequently observed. It also affects the contractility of the heart, the heart rhythm and blood flow to the kidneys. For some time, the significance of endothelin in various cancers, especially prostate and breast cancer are discussed.

Receptors

Endothelin mediates its effects via G protein - coupled receptors, the endothelin receptors. Currently, two of the endothelin receptor subtypes are known, which are referred to as ETA and ETB. ETA receptors can be found among others in smooth muscle cells of blood vessels, where they are responsible for the vasoconstriction caused by endothelin -1. Contrast, ETB receptors on endothelial cells, epithelial cells (ET- B1) and smooth muscle cells ( ET -B2) detectable. Activation of endothelial ETB receptors by endothelin -1 or endothelin-3 can be both a vasodilatation: have the effect of (ET- B1 through the release of nitric oxide (NO ) ), and vasoconstriction (ET- B2).

Endothelin antagonists

Antagonists of endothelin (eg ambrisentan, atrasentan, bosentan, Clazosentan, Macitentan and Thelin ) are currently being used successfully as an orphan drug in the treatment of Pulmonary Hypertension. Another application could be the therapy of heart failure in the future. However, the substances disappointed here so far, despite promising results in animal studies to clinical application. The last study, the so-called EARTH Trial, 2004 was terminated because no improvement of symptoms in the patients treated had occurred.

Human Genome Organisation Protein isoform Pulse Smooth muscle tissue Epithelium Receptor antagonist Sitaxentan
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