Properties of an endothelin-3-sensitive Eta-like endothelin receptor in brain capillary endothelial cells.

[125I]Et-1 binding experiments showed the presence in rat brain capillary endothelial cells of typical ETA receptors that recognized Et-1, BQ-123 and FR139317 but not IRL1620, [Ala1,3.11,15]ET-1 or Et-3. [125I]Et-3 binding experiments showed that the same cells expressed high affinity Et-3 binding sites (Kd=1 nM) that recognized Et-1] (Kd=1 nM), BQ-123 (Kd = 5 nM) and FR139317 (Kd=2 nM) but not low concentrations of IRL1620 or of [Ala 1,3,11,15]Et-1. Et-3 activated N+/H+ exchange activity in a manner that was sensitive to BQ-123 (Ki=6 nM) and FR 139317 (Ki = 0.6 nM). The results suggest the existence of a high affinity Et-3 receptor that is insensitive to ETB receptor agonists and sensitive to ETA receptor antagonists and that is functionally coupled to Na+/H+ exchange activity.