Endothelin receptor synthetic N-terminal fragment interacts with the receptor itself.
Endothelin binds to receptors belonging to the family of G-protein-coupled receptors with an N-terminal extracellular domain that is suspected to be part of the binding site. We have synthesized different peptides 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 not able to compete with radiolabeled ET-1 binding. The agonist effect was inhibited by the ET receptor antagonists PD 142893 and BQ123, suggesting an interaction between Nt (20-79) and the ETA receptor at a site that could be different from the one of ET-1.
Mendre
C
C
INSERM, U401, Centre de Pharmacologie-Endocrinologie, Montpellier, France.
Hamroun
D
D
Dupoirieux
L
L
Calas
B
B
Chevillard
C
C
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000037:antagonists & inhibitors*; D006801:Humans; D008533:Megakaryocytes / Q000378:metabolism*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology; D011485:Protein Binding; D011487:Protein Conformation; D017466:Receptors, Endothelin / Q000378:metabolism*
D019332:Endothelin-1; D010446:Peptide Fragments; D017466:Receptors, Endothelin; D002118:Calcium