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Abstract

Local endocrine factors (autacoids, paracrine agents), which are secreted from vessel’s endothelium, provide to arrange of vascular tonus. Some of these factors cause vessel relaxation (vasodilator) such as nitric oxide (NO) and prostaglandin-I2 (PGI2); some others cause vessel spasm (vasoconstrictor) such as endothelin (ET)-1 and angiothensin-II. Described in 1988 by Yanagisawa and at al., ET-1 synthesized in vessel endothelium; with its long lasting effect and slow releasing, it is presently one of the strongest vasoconstrictor agents contrary to NO. ET, derived from vessel endothelium is ubiquitous peptide, acts as promitogens and plays an important role during embryonic development. Existence of three distinct genes for ET has been determined which are called ET-1, ET-2, ET-3 and encodes three distinct peptides. However, ET-1 is the isopeptide which is found in greatest concentration in the blood and mainly synthesized by the human endothelium. All three ET isoforms include four cysteine residues, which connect to disulphide bonding (Cys1-Cys15; Cys3-Cys11). ET-1, which has twenty-one amino acids residue, realizes biological effects via cell surface ETA and ETB reseptors, which are 7-transmembrane receptors coupled to G-proteins. ET receptor antagonists submit a new therapeutic area for serious diseases such as congestive heart failure, pulmonary hypertension, arterial hypertension, prostate hypertrophy, prostate cancers, preeclampsia, atherosclerosis and renal failure

Keywords

• Endothelins, endothelin-1, endothelin receptor antagonists, autacoids

Endotelinler: Vazoaktif Peptidler

Öz

Damar endotelyumundan salgılanan lokal hormonal faktörler (otokoidler, parakrin ajanlar) damar tonusunun düzenlenmesini sağlarlar. Bu faktörlerden nitrik oksit (NO), prostaglandin-I2 (PGI2) gibi bir kısmı damar gevşetici (vazodilatatör) olarak düzenleme yapar, endotelin (ET)–1, anjiotensin-II gibi diğer bir kısmı da damar büzücü (vazokonstriktör) olarak işlev görür. Yanagisawa ve ark. tarafından 1988 yılında tanımlanan, damar endotelyumundan sentezlenen ET–1; NO’nun aksine, uzun etki süresi ve yavaş salınımı ile, bilinen en güçlü vazokonstriktör ajanlardan biridir. Damar endotelyumundan kaynaklanan ET insan vücudunda hemen her yerde bulunur, promitojen olarak etki eder ve embriyonik gelişimde önemli bir rol oynar. ET için üç ayrı peptidi kodlayan ve ET–1, ET–2, ET–3 olarak adlandırılan üç farklı genin varlığı saptanmıştır. Ancak kanda en yüksek konsantrasyonda bulunan ve insan endotelyumu tarafından başlıca sentezlenen izopeptid ET-1’dir. Her üç ET isoformu, aralarında disülfit bağının yer aldığı (Cys1 - Cys15; Cys3 -Cys11) dört sistein rezidüsü içerir. Yirmi bir amino asit rezidüsüne sahip ET-1, biyolojik etkilerini G proteinine bağlı zarı 7 defa geçen ETA ve ETB reseptörleri aracılığıyla gerçekleştirir. ET reseptör antagonistleri konjestif kalp yetmezliği, pulmoner hipertansiyon, arteryel hipertansiyon, prostat hipertrofisi, prostat kanserleri, preeklamsi, ateroskleroz ve böbrek yetmezliği gibi ciddi hastalıklar için yeni bir tedavi edici saha sunmaktadır.

Anahtar Kelimeler

• Endotelin, endotelin–1, endotelin reseptör antagonistleri, otakoidler

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