title: Comparison of PD 145065 and Ro 46-2005 as antagonists of contractions of guinea-pig airways induced by endothelin-1 or IRL 1620.
abstract: Cumulative concentrations of endothelin-1 or IRL 1620 (Suc-[Glu9,Ala11,15]endothelin-1-(8-21)), and endothelin ETB receptor selective agonist were similarly potent in contracting guinea-pig upper bronchi, whereas endothelin-1 was more potent than IRL 1620 in contracting lung parenchymal strips. PD 145065 (10(-5) M and 10(-4) M), a non-selective endothelin ETA/ETB receptor antagonist (Ac-D-Bhg-L-Leu-L-Asp-L-Ile-L-Ile-L-Trp), significantly attenuated the contractions induced by endothelin-1 in either preparation whereas Ro 46-2005 (3 x 10(-5) M and 10(-4) M), a non-peptide non-selective receptor antagonist (4-tert-butyl-N-[6-(2-hydroxy-ethoxy)-5-3-methoxy-phenoxy)-4-pyrimidinyl (benzenesulfonamide)), was without effect. PD 145065 (10(-6) M and 10(-5) M) also strongly inhibited contractions induced by IRL 1620, whereas Ro 46-2005 caused much less antagonism. Thus, PD 145065 is a more potent antagonist than Ro 46-2005 of contractions induced by endothelin-1 or IRL 1620 and mediated by endothelin ETB receptors in these guinea-pig airway preparations.
authors.affiliation: William Harvey Research Institute, St. Bartholomew's Hospital Medical College, Charterhouse Square, London, UK.
authors.forename: B
authors.initials: B
authors.lastname: Battistini
authors.forename: T D
authors.initials: TD
authors.lastname: Warner
authors.forename: A
authors.initials: A
authors.lastname: Fournier
authors.forename: J R
authors.initials: JR
authors.lastname: Vane
mesh_terms: D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects*; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D006168:Guinea Pigs; D008168:Lung / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009842:Oligopeptides / Q000494:pharmacology*; D010446:Peptide Fragments / Q000037:antagonists & inhibitors*; D011743:Pyrimidines / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*; D000096926:Benzenesulfonamides
chemical_list: D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D009842:Oligopeptides; D010446:Peptide Fragments; D011743:Pyrimidines; D013449:Sulfonamides; C074308:sovateltide; C083751:Ro 46-2005; D000096926:Benzenesulfonamides; C082887:PD 145065