Pharmacology of endothelins: vascular preparations for studying ETA and ETB receptors.
Three rabbit vessels, the carotid and pulmonary arteries and the jugular vein were investigated to identify vascular monoreceptor systems (either ETA or ETB) to be used in structure-activity studies on endothelins and their antagonists. The RbCA has been found to behave as a monoreceptor ETA preparation, since it shows much greater sensitivity to ET-1 than to ET-3 and is insensitive to IRL 1620. The contractile response of the RbCA to ET-1 is reduced in the presence of BQ-123 but is not influenced by BQ-788. The RbPA behaves as a pure ETB system when stimulated with the ETB selective agonist IRL 1620. The contractile effect of IRL 1620 is reduced in the presence of BQ-788 but is not influenced by BQ-123. The RbJV responds to ET-1 and to IRL 1620 with contractions that are reduced by both BQ-123 and BQ-788, respectively. THe RbJV appears to be a mixed ETA and ETB system in which the two functional sites play an equivalent role in the stimulatory contractile response. Thus, contractile ETA and ETB receptors have been found in arterial and venous vessels of the rabbit and some of these vessels provide sensitive and selective (either ETA or ETB) preparations that appear to be adequate for pharmacological studies on ET receptor agonists or antagonists.
Caló
G
G
Institute of Pharmacology, University of Ferrara, Italy.
Gratton
J P
JP
Télémaque
S
S
D'Orléans-Juste
P
P
Regoli
D
D
D000818:Animals; D002339:Carotid Arteries; D004305:Dose-Response Relationship, Drug; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000494:pharmacology*; D066298:In Vitro Techniques; D007601:Jugular Veins; D007700:Kinetics; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009842:Oligopeptides / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D011651:Pulmonary Artery; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000502:physiology*; D013997:Time Factors
D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D009842:Oligopeptides; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D010880:Piperidines; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; C074308:sovateltide; C086539:BQ 788; C072247:cyclo(Trp-Asp-Pro-Val-Leu)