1 Introduction

Endothelin (EDN) is a vasoactive substance with strong vasoconstriction effect isolated from cultured porcine aortic endothelial cells in 1988 by Yanagisawa et al. It participates in the normal physiological functions and the pathophysiological processes of these diseases through autocrine, paracrine or endocrine effects. EDN is mainly distributed in the cardiovascular endothelial cell system, and is also widely found in organs, tissues, such as the lungs, brain, liver, and skin.

2 Structure and Classification

EDN is composed of 21 amino acids and it’s molecular weight is about 2492Da. The C-terminus and the N-terminus are free tryptophan and cysteine respectively. There are two disulfide bonds inside the molecule. The bicyclic structure formed by the disulfide bond is a key factor in maintaining the stability of the spatial structure of EDN molecules and molecular activity. According to the amino acid sequence of endothelin, it is divided into three isoforms: EDN1, EDN2 and EDN3. Structurally, EDN1 and EDN2 differ only by 2 amino acids, EDN3 and EDN1 differ by 6 amino acids, but their 7 C-terminal amino acids are idEDNical. Endothelin gene expression has differEDN tissue specificity. Human EDN1 molecules are mainly expressed in vascular endothelial cells; EDN2 and EDN3 are mainly expressed in neural tissues.

The EDN3 gene is located on chromosome 20q13.2-13.3. EDN3 contains 21 amino acids having a molecular mass of 2643.08 Dalton, and the molecular formula is: C121H168N26O33S4. Disulfide bonds between cys-1 and cys-15 + cys-3 and cys-11. EDN3 has different affinities for EDN receptors EDNAR and EDNBR. The affinity of EDN3 for EDNAR is much lower than EDN1 and EDN2 for EDNAR. While affinity of EDNBR is compatible with all endothelin-related peptides.

3 Function

EDN3 interacts with endothelin receptor B(EDNRB),on the surface of cells. Throughout embryonic developmEDN,EDN3 takes part in neural crest cells that migrate from the developing spinal cord to specific regions in the embryo,where they give rise to many different EDN types of cells. EDN3 and EDN3R are necessary for the formation of nerves in the large intestine (EDNeric nerves) and melanocytes (produce melanin). Mutations in the EDN3 gene is linked with Waardenburg syndrome, type IV that is characterized by changes in skin, hair, and eye coloring. Mutations in the EDN3 gene is linked with Hirschsprung disease that causes severe constipation or intestinal blockage.

4 Involvement of disease

Hirschsprung's disease (HD)

EDN3 binds to EDNRB and transmits information into the cell through the intracellular Ca2+ phospholipid-dependent protein kinase second messenger system, which promotes the rapid release of Ca2+ in the endoplasmic reticulum and sarcoplasmic reticulum, and the intracellular Ca2+ concentration increases rapidly.

During embryonic development, EDNRB/ET-3 plays an important role in the migration and differentiation of neural crest cells into ganglion cells, which is indispensable for the formation of colorectal and intestinal nervous system.

Breast cancer

Endothelin (EDN) is a cytokine that includes EDN1, EDN2 and EDN3. It‘s conduction system plays an important role in cell proliferation, differentiation and metastasis. Many studies have shown that changes in EDN conduction system can lead to tumors. The abnormality of the EDN signal transduction system can regulate the survival rate of cells, enhance the invasiveness of cells, and cause pathological changes in tissues or organs to leading to tumors.

Author's Bio: 

EDNRB involved in several pathways and played different roles in them. We selected most pathways EDNRB participated on our site, such as Arf6 trafficking events, Calcium signaling pathway, Class A/1 (Rhodopsin-like receptors), which may be useful for your reference. Also, other proteins which involved in the same pathway with EDNRB were listed below. Creative Biomart supplied nearly all the proteins listed, you can search them on our site.