Effects of endothelin receptor selective antagonists, BQ-123 and BQ-788, on IRL 1620 and endothelin-1 responses of airway and vascular preparations from rats.
IRL 1620 (Suc-[Glu9, Ala11,15]ET-1(8-21), a selective ETB receptor agonist) contracted rat trachea and bronchus. The maximum response to IRL 1620 was less than that to endothelin-1 (ET-1) and, compared with ET-1 responses, IRL 1620 responses reached equilibrium more quickly. IRL 1620 responses were antagonized by the selective ETB antagonist, BQ-788 (3 microM), but not by the selective ETA antagonist, BQ-123 (3 microM). ET-1 concentration-response curves were shifted only in the presence of both BQ-123 and BQ-788 (3 microM). In the presence of BQ-123, the time course of ET-1 responses changed from being slow and sustained (ETA, see below) to being more like that to IRL 1620 (ETB). IRL 1620 did not contract pulmonary artery preparations from rats but ET-1 produced slow and sustained contractile responses which were antagonized by BQ-123 but not by BQ-788. Thus, ET-1 contracts rat pulmonary artery and aorta predominantly via ETA receptors (responses blocked by BQ-123) and functional ETB receptors are unlikely to be present (no responses to IRL 1620). In contrast, ET-1 contracts rat trachea and bronchus via ETA and ETB receptors (tissues contracted to IRL 1620, ET-1 responses were blocked by a combination of BQ-123 and BQ-788 and ET-1 responses resembled ETB in character when ETA receptors were blocked.
Department of Physiology and Pharmacology, University of Queensland, Brisbane, Australia.
S R
SR
O'Donnell
C S
CS
Kay
D000818:Animals; D001980:Bronchi / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009842:Oligopeptides / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D014132:Trachea / Q000187:drug effects* / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects*
D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D009842:Oligopeptides; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D010880:Piperidines; C074308:sovateltide; C086539:BQ 788; C072247:cyclo(Trp-Asp-Pro-Val-Leu)