Influence of regional differences in ET(A) and ET(B) receptor subtype proportions on endothelin-1-induced contractions in porcine isolated trachea and bronchus

Roy Goldie, A.C. D'Aprile, R. Cvetkovski, Paul Rigby, Peter Henry

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

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 [I-125]-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).4 In trachea, endothelin-1 induced contractions were not significantly inhibited by either the ET(A) receptor-selective antagonist, BQ-123 (3 mu M) or the ET(B) receptor-selective antagonist, BQ-788 (1 mu M). However, in the combined presence of BQ-123 and BQ-788, the concentration-effect curve to endothelin-1 was shifted to the right by 3.7 fold (n=8; P=0.01).5 In bronchus, concentration-effect curves to endothelin-1 were shifted to the right by BQ-123 (3 mu M; 4.3 fold; P
Original languageEnglish
Pages (from-to)736-742
JournalBritish Journal of Pharmacology
Volume117
DOIs
Publication statusPublished - 1996

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