COMPETITIVE AND NONCOMPETITIVE INTERACTIONS OF BQ-123 WITH ENDOTHELIN ET(A) RECEPTORS

BQ-123 (cyclo[D-Trp-D-Asp-Pro-D-Val-Leu]) is a competitive antagonist of the ET(A) receptor subtype for endothelins in aortic myocytes, and a non-competitive antagonist in human neuroblastoma cells. In the present study, using indo-I loaded rat brain capillary endothelial cells, we demonstrate that BQ-123 acts either as a competitive or as a non-competitive antagonist of endothelin-I 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 ET(A) receptors that are, however, less stable than the complexes formed by endothelin-1 and ET(A) receptors.