Premium
Relationship between endothelin‐1 binding site densities and constrictor activities in human and animal airway smooth muscle
Author(s) -
Henry Peter J.,
Rigby Paul J.,
Self Glenn J.,
Preuss Janet M.,
Goldie Roy G.
Publication year - 1990
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1990.tb14093.x
Subject(s) - guinea pig , bronchus , carbachol , anatomy , endothelin 1 , biology , submucosal glands , binding site , endocrinology , dissociation constant , smooth muscle , medicine , microbiology and biotechnology , chemistry , lung , respiratory disease , receptor , biochemistry , secretion , stimulation
1 Endothelin‐1 (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 μ m ET‐1 (measured as the % maximum response to 10 μ m carbachol, % C max ± s.e.mean) and the mean concentration of ET‐1 producing 30% (95% confidence limits) were respectively; 85.9 ± 5.4% and 3.4n m (2.4–5.0) for mouse trachea (n = 11), 88.8 ± 4.7% and 18.2 n m (11.2–25.2) for rat trachea (n = 6), 71.0 ± 7.1% and 35.2 n m (5.4–231) for human bronchus ( n = 3), and 32.3 ± 3.0% and 241 n m (125–460) for guinea‐pig trachea ( n = 6). 3 Light microscopic autoradiography revealed specific [ 125 I]‐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 I]‐ET‐1 binding (0.1–2n m ) 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 [ 125 I]‐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 [ 125 I]‐ET‐l 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‐oxygenaseor epithelium‐derived constrictor substances, but may have been due to an inter‐species difference in the receptor‐effector system for ET‐1.