Endothelin and structurally related analogs distinguish between endothelin receptor subtypes

• Published in: Biochemical and biophysical research communications Vol. 183; no. 2; pp. 566 - 571
• Main Authors: Panek, Robert L., Major, Terry C., Hingorani, Gary P., Doherty, Annette M., Taylor, David G., Rapundalo, Stephen T.
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 16.03.1992; Elsevier
• Subjects: Aminoacids, peptides. Hormones. Neuropeptides; Analytical, structural and metabolic biochemistry; Animals; Binding, Competitive; Biological and medical sciences; Dose-Response Relationship, Drug; Endothelins - metabolism; Endothelins - pharmacology; Fundamental and applied biological sciences. Psychology; Proteins; Rabbits; Rats; Receptors, Cell Surface - classification; Receptors, Cell Surface - drug effects; Receptors, Endothelin; Viper Venoms - metabolism; Viper Venoms - pharmacology; Endothelin; Rat; Peptide hormone; Rodentia; Pulmonary artery; Thoracic aorta; Vertebrata; Membrane receptor; Mammalia; Binding capacity; Synthetic product; Structure activity relation; Analog; Vasoconstrictor agent
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/0006-291X(92)90519-Q

The endothelin (ET) analog ET-1[1,3,11,15-Ala] was compared with ET-1, ET-2, ET-3 and sarafotoxins (SRTX) S6b and S6c for receptor binding and function. All the peptides exhibited high affinity binding and contracted rabbit pulmonary artery with near equal potency. In rat aorta both ET-3 and ET-1 [1,3,11,15-Ala] bound with much lower affinity than ET-1 while ET-3 displayed weak contractile potency and ET-1[1,3,11,15-Ala] and SRTX-c were inactive. In rat left atria, ET-1[1,3,11,15-Ala] and SRTX-c were weak inhibitors of binding and were also functionally inactive, whereas ET-1, ET-2, ET-3, and SRTX-b were equipotent in producing contractile responses. The data support the idea of there being a predominance of ET A receptors in rat aorta and ET B receptors in rabbit pulmonary artery. In rat left atria, the ET receptor could not be readily classified into ET A or ET B and suggests the existence of a new receptor subtype.