The endothelin system is comprised of three active peptides, ET-1, 2, and 3, which are considered to be very powerful vasoconstrictive substances. In humans, endothelins mediate their actions via two specific G-Protein Coupled Receptors, ET_AR and ET_BR. Both ET_AR and ET_BR are present in heart and in human myocardium at similar levels.^1,2

The endothelin receptors differ in their ligand specificity. While ET_AR has varying affinities for the endothelin isoforms (ET-1 >ET-2>ET-3), ET_BR shows no selective affinity.^2,3 Subsequent studies have demonstrated the presence of endothelins in vascular as well as in non-vascular cells and tissues, having multiple biological activities.

Currently, there is increasing evidence that ET-1 may modulate mitogenesis, apoptosis, angiogenesis tumor invasion and the development of metastases.³

Overexpression of ET-1 and ET_AR was reported in different malignancies including prostate cancer human Kaposi’s sarcoma, ovarian and breast carcinomas.⁴

In breast carcinomas overexpression of ET-1 and ET_A receptors correlated with parameters that characterize aggressive types of breast cancer suggesting that analysis of ET_AR expression might be used as a diagnostic marker for evaluating the progression of the disease and effectiveness of treatment. These and other findings have made ET receptors, and especially ET_AR, promising therapeutic targets for pharmacological intervention.^5-9