Competitive and non competitive interactions of BQ-123 with endothelin ETA receptors.
BQ-123 (cyclo[D-Trp-D-Asp-Pro-D-Val-Leu]) is a competitive antagonist of the ETA receptor subtype for endothelins in aortic myocytes, and a non-competitive antagonist in human neuroblastoma cells. In the present study, using indo-1 loaded rat brain capillary endothelial cells, we demonstrate that BQ-123 acts either as a non-competitive antagonist of endothelin-1 action on [Ca2+]i depending on the experimental conditions used. A simple hypothesis to account for these results is that BQ-123 forms stable complexes with ETA receptors that are, however, less stable than the complexes formed by endothelin-1 and ETA receptors.
Vigne
P
P
Institut de Pharmacologie Moléculaire et Cellulaire du CNRS, Sophia Antipolis, Valbonne, France.
Breittmayer
J P
JP
Frelin
C
C
D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000098:blood supply; D002118:Calcium / Q000378:metabolism; D002196:Capillaries; D002478:Cells, Cultured; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008969:Molecular Sequence Data; D010456:Peptides, Cyclic / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017466:Receptors, Endothelin / Q000378:metabolism
D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D010456:Peptides, Cyclic; D017466:Receptors, Endothelin; C072247:cyclo(Trp-Asp-Pro-Val-Leu); D002118:Calcium