RESUMO
The kinetics of action of two selective leukotriene (SRS-A) antagonists, FPL 55712 and FPL 59257, on guinea pig isolated ileum were examined by measuring pA2, pD'2 and the rate constants K1, K2, Ke and Kon. FPL 55712 was shown to be a competitive antagonist, producing a parallel displacement of dose response curves to LTD4 with no depression of the maximum. FPL 59257, however, was shown to be a non-competitive antagonist which depressed the maximum response to LTD4 and yielded a Schild plot slope significantly less than unity. FPL 59257 has a slower onset and greater duration of action than FPL 55712, as reflected in the rate constants K2 and Kon. The implications of these results are discussed.
Assuntos
Cromonas/farmacologia , Contração Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , SRS-A/antagonistas & inibidores , Animais , Cobaias , Íleo/efeitos dos fármacos , Técnicas In Vitro , Cinética , MasculinoAssuntos
Cromonas/farmacologia , Pulmão/fisiologia , Contração Muscular/efeitos dos fármacos , Músculo Liso/fisiologia , SRS-A/antagonistas & inibidores , Animais , Brônquios/fisiologia , Cobaias , Humanos , Pulmão/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , SRS-A/farmacologia , Relação Estrutura-Atividade , Traqueia/fisiologiaRESUMO
1 The responses of human isolated bronchial and lung parenchymal strips to cumulative doses of slow reacting substance of anaphylaxis (SRS-A), histamine, prostaglandin F2 alpha (PGF2 alpha) and acetylcholine have been examined, after storing the tissues overnight in Krebs solution at 4 degrees C. 2 Both tissues contracted to all four agonists. The order of potency (as determined by height of maximal contraction) was: bronchial strip: acetylcholine greater than histamine = PGF2 alpha greater than SRS-A, and parenchymal strip: PGF2 alpha much greater than histamine = SRS-A greater than acetylcholine. 3 Maximal contractions to SRS-A of both the human bronchial and parenchymal strips were approx. 30% of the maximal contractions produced by the most potent agonist on each tissue (PGF2 alpha on the parenchymal strip and acetylcholine on the bronchial strip). SRS-A, therefore, does not have a powerful direct contractile effect on either parenchymal or bronchial strip of human lung, and is approximately equipotent on both tissues. A part of the broncho-constrictor activity of SRS-A in vivo may be mediated via indirect pathways. 4 The selective SRS-A antagonist, FPL 55712, was approximately equipotent in antagonizing contractions induced by SRS-A on both human bronchial and parenchymal strips.