T. Takahashi, P. Barnes, I. Kawikova
Apr 1, 1997
Citations
2
Influential Citations
22
Citations
Quality indicators
Journal
European journal of pharmacology
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.