DISTRIBUTION OF BETA-1-ADRENOCEPTORS AND BETA-2-ADRENOCEPTORS IN MOUSE TRACHEA AND LUNG - A QUANTITATIVE AUTORADIOGRAPHIC STUDY

Binding and quantitative autoradiography were used to detect [125I]-idiocyanopindolol (I-CYP) associated with β1- and β2-adrenoceptors in mouse tracheal epithelium and airway smooth muscle as well as in lung parenchymal tissue. Specific I-CYP binding to slide-mounted tissue sections of both trachea and parenchyma was of high affinity (K(D) = 49.0 pM, n = 3, trachea; K(D) = 118.9 pM, n = 3, parenchyma) and saturable, involving single populations of non-interacting binding sites (Hill coefficient nH = 1.00 ± 0.02, trachea; nH = 0.99 ± 0.03, parenchyma). Direct measurement of tissue radioactivity also showed that specific I-CYP binding was competitively inhibited in the presence of the β-adrenoceptor antagonists (-)-propranolol (non-selective), CGP 20712A (β1-selective) and ICI 118,551 (β2-selective). Analysis of the competition binding curves for the two selective antagonists revealed mixed populations of β1- and β2-adrenoceptors in the approximate proportions 33% and 67% respectively in mouse trachea and 28% and 72% respectively in mouse lung parenchyma. Densities of autoradiographic grains derived from specific I-CYP binding to alveolar wall tissue and to tracheal epithelium and airway smooth muscle were quantified by a computer-assisted image analysis system, which allowed the construction of competition binding curves in the presence of the selective β-adrenoceptor antagonists CGP 20712A and ICI 118,551. Analysis of these data demonstrated that in alveolar wall, β1- and β2-adrenoceptors co-existed in the proportions 18% and 82%, respectively. Quantitative autoradiographic analyses also showed that β1- and β2-adrenoceptors were differentially distributed in tracheal epithelium and airway smooth muscle. The β2-adrenoceptor subtype accounted for 71% of all β-adrenoceptors in epithelium. Conversely, β1-adrenoceptors which mediate relaxant responses of mouse trachea to β-adrenoceptor agonists (Henry and Goldie, 1990), accounted for 69% of all β-adrenoceptors in the airway smooth muscle.