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.
Vigne
P
P
Institut de Pharmacologie Moléculaire et Cellulaire du CNRS, Université de Nice-Sophia Antipolis, Valbonne, France.
Desmarets
J
J
Guedin
D
D
Frelin
C
C
D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D001921:Brain / Q000098:blood supply*; D002196:Capillaries; D016232:Endothelins / Q000378:metabolism* / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D051381:Rats; D017466:Receptors, Endothelin / Q000187:drug effects / Q000378:metabolism*; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism
D016232:Endothelins; D017466:Receptors, Endothelin; D017923:Sodium-Hydrogen Exchangers; C098996:endothelin-3 receptor