title: Contraction of human airway smooth muscle by endothelin-1 and IRL 1620: effect of bosentan.
abstract: We have examined whether 4-tert-butyl-N-[6-(2-hydroxy-ethoxy)-2,2'-bipyrimidin-4-yl]-benzen esulfonamide (bosentan; endothelin ET(A/B) receptor antagonist) and (R)2-[(R)-2-[(S)-2-[[1-(hexahydro-1H-azepinyl)]carbonyl] amino-4-methylpentanoil]amino-3-[3-(1-methyl-1H-indoyl)]prop ionyl]amino-3-(2-pyridyl) propionic acid (FR 139317; endothelin ET(A) receptor antagonist) inhibit contractions of human airway smooth muscle induced by endothelin-1 or Suc-[Glu9,Ala(11,15)]enthothelin-1-(8-21) (IRL 1620; endothelin ET(B) receptor agonist). Endothelin-1 and IRL 1620 were equipotent. Bosentan and FR 139317 (each 10 microM) produced a small shift in response curves to endothelin-1 (1.6- and 1.5-fold, respectively). However, bosentan was more potent against contractions elicited by IRL 1620 (10 microM, 11.2-fold shift) suggesting that these agonists exhibit different kinetic interactions with endothelin receptors or implying an interaction with a novel endothelin ET(B) receptor subtype in human airways.
authors.affiliation: Thoracic Medicine, Imperial College School of Medicine at the National Heart and Lung Institute, London, UK.
authors.forename: T
authors.initials: T
authors.lastname: Takahashi
authors.forename: P J
authors.initials: PJ
authors.lastname: Barnes
authors.forename: I
authors.initials: I
authors.lastname: Kawikova
authors.forename: M H
authors.initials: MH
authors.lastname: Yacoub
authors.forename: T D
authors.initials: TD
authors.lastname: Warner
authors.forename: M G
authors.initials: MG
authors.lastname: Belvisi
mesh_terms: D000293:Adolescent; D000328:Adult; D000077300:Bosentan; D001980:Bronchi / Q000187:drug effects*; D002648:Child; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000494:pharmacology*; D016232:Endothelins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*
chemical_list: D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D016232:Endothelins; D010446:Peptide Fragments; D013449:Sulfonamides; C074308:sovateltide; D000077300:Bosentan