Relationship between endothelin‐1 binding site densities and constrictor activities in human and animal airway smooth muscle

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Abstract
1 Endothelin- (ET-1) binding site densities and constrictor activities were compared in airway smooth muscle preparations of human, guinea-pig, rat and mouse. 2 The mean contractile response to 0.3 .mu.M ET-1 (measured as the % maximum response to 10 .mu.M carbachol, % Cmax .+-. s.e.mean) and the mean concentration of ET-1 producing 30% Cmax (95% confidence limits) were respectively; 85.9 .+-. 5.4% and 3.4 nM (2.4-5.0) for mouse trachea (n = 11), 88.8 .+-. 4.7% and 18.2 nm (11.2-25.2) for rat trachea (n = 6), 71.0 .+-. 7.1% and 35.2 nM (5.4-231) for human bronchus (n = 3), and 32.3 .+-. 3.0% and 241 nM (125-460) for guinea-pig trachea (n = 6). 3 Light microscopic autoradiography revealed specific [125I]-ET-1 binding sites localized to the smooth muscle band, with very low levels of binding associated with cartilage, submucosal and epithelial cells. 4 Quantitative autoradiographic analyses of the concentration-dependence of specific [125]-ET-1 binding (0.1-2 nM) to smooth muscle revealed similar dissociation constants but markedly different specific binding site densities for the various animal species. The order of densities of specific [125I]-ET-1 binding sites was rat trachea (69.0 .+-. 11.2 amol mm-2) > human bronchus (42.7 .+-. 17.5 amol mm-2) > mouse trachea (28.7 .+-. 2.6 amol mm-2) > guinea-pig trachea (8.3 .+-. 1.8 amol mm-2). 5 A positive relationship between [125I]-ET-1 binding site density and ET-1 constrictor activity was observed in airway smooth muscle preparations from rat, human and guinea-pig. The greater sensitivity of mouse trachea to the constrictor actions of ET-1 was not dependent on the release of cyclo-oxygenase-or epithelium-derived constrictor substances, but may have been due to an inter-species difference in the receptor-effector system for ET-1.