Species difference in the binding characteristics of RES-701-1: potent endothelin ETB receptor-selective antagonist.

Species-dependency of RES-701-1 (cyclic (Gly1-Asp9)(Gly-Asn-Trp-His-Gly-Thr-Ala-Pro-Asp-Trp-Phe-Phe- Asn-Tyr-Tyr-Trp)) has been shown using 125I-ET-1 binding to membranes from various animal tissues. RES-701-1 selectively inhibited the 125I-ET-1 binding to ETB receptor from canine, rabbit, porcine, and guinea pig lung tissues in a dose-dependent manner with IC50 values of 60 nM, 20, 4 nM and 13 nM, respectively. Though RES-701-1 retained selectivity for ETB receptor even at higher concentrations, RES-701-1 inhibited the 125I-ET-1 binding to ETB receptor from rat lung, heart, and kidney only weakly; IC50 values were calculated to be 1.2 microM, 0.9 microM and 0.6 microM, respectively. These results suggest that RES-701-1 is a potent and specific antagonist for ETB receptor in various species of animal, and would be a powerful tool for understanding the physiological roles of ETB receptor, but care must be taken in use of RES-701-1 in experiments with rat.