ENDOTHELIN RECEPTOR SYNTHETIC N-TERMINAL FRAGMENT INTERACTS WITH THE RECEPTOR ITSELF

Endothelin binds to receptors belonging to the family of G-protein-cou pled receptors with an N-terminal extracellular domain that is suspect ed to be part of the binding site. We have synthesized different pepti des of this N-terminal extracellular domain and analyzed the increase in calcium concentration ([Ca2+](i)) induced by these peptides in the MEG-01 cell line and their influence on the ET-1 concentration-effect response. Nt(20-79) exhibited a partial agonistic effect on [Ca2+](i) and blunted the functional response of ET-1 in MEG-01 cells, but was n ot able to compete with radiolabeled ET-1 binding. The agonist effect was inhibited by the ET receptor antagonists PD142893 and BQ123, sugge sting an interaction between Nt(20-79) and the ET(A) receptor at a sit e that could be different from the one of ET-1.