Influence of regional differences in ET_A and ET_B receptor subtype proportions on endothelin-1-induced contractions in porcine isolated trachea and bronchus

摘要

1 Quantitative autoradiographic studies were conducted to determine the distributions and densities of ET_A and ET_B binding site subtypes in porcine tracheal and bronchial smooth muscle. In addition, the roles of ET_A and ET_B receptors in endothelin-1-mediated contraction of these tissues were assessed. 2 Quantitative autoradiographic studies revealed that both ET_A and ET_B binding sites for [~(125)I]-endothelin-1 were present in both bronchial and tracheal airway smooth muscle. However, the proportions of these sites were markedly different at these two levels within the respiratory tract. In tracheal smooth muscle, the proportions of ET_A and ET_B sites were 30 ± 1% and 70 ± 1% respectively, whereas in bronchial smooth muscle, these proportions were virtually reversed, being 73 ± 2% and 32 ± 8% respectively. 3 Endothelin-1 induced concentration-dependent contraction of porcine tracheal and bronchial airway smooth muscle. Endothelin-1 had similar potency (concentration producing 30% of the maximum carbachol contraction, C_(max)) in trachea (22 nM; 95% confidence limits (c.l.), 9-55 nM; n = 9) and bronchus (22 nM; c.l., 9-55 nM; n = 6). Endothelin-1 also produced comparable maximal contractions in trachea (59 ± 5% C_(max); n = 9) and bronchus (65 ± 4% C_(max), n = 6).