Distribution of beta 1- and beta 2-adrenoceptors in mouse trachea and lung: a quantitative autoradiographic study.
1. Binding and quantitative autoradiography were used to detect [125I]-iodocyanopindolol (I-CYP) associated with beta 1- and beta 2-adrenoceptors in mouse tracheal epithelium and airway smooth muscle as well as in lung parenchymal tissue. 2. Specific I-CYP binding to slide-mounted tissue sections of both trachea and parenchyma was of high affinity (KD = 49.0 pM, n = 3, trachea; KD = 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). 3. Direct measurement of tissue radioactivity also showed that specific I-CYP binding was competitively inhibited in the presence of the beta-adrenoceptor antagonists (-)-propranolol (non-selective), CGP 20712A (beta 1-selective) and ICI 118,551 (beta 2-selective). Analysis of the competition binding curves for the two selective antagonists revealed mixed populations of beta 1- and beta 2-adrenoceptors in the approximate proportions 33% and 67% respectively in mouse trachea and 28% and 72% respectively in mouse lung parenchyma. 4. 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 beta-adrenoceptor antagonists CGP 20712A and ICI 118,551. Analysis of these data demonstrated that in alveolar wall, beta 1- and beta 2-adrenoceptors co-existed in the proportions 18% and 82%, respectively. 5. Quantitative autoradiographic analyses also showed that beta 1- and beta 2-adrenoceptors were differentially distributed in tracheal epithelium and airway smooth muscle. The beta 2-adrenoceptor subtype accounted for 71% of all beta-adrenoceptors in epithelium. Conversely, beta l-adrenoceptors which mediate relaxant responses of mouse trachea to beta,-adrenoceptor agonists (Henry & Goldie, 1990), accounted for 69% of all beta-adrenoceptors in the airway smooth muscle.
Henry
P J
PJ
Department of Pharmacology, University of Western Australia, Perth, Nedlands.
Rigby
P J
PJ
Goldie
R G
RG
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D007093:Imidazoles / Q000494:pharmacology; D007457:Iodine Radioisotopes; D020120:Iodocyanopindolol; D007700:Kinetics; D008168:Lung / Q000033:anatomy & histology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D010869:Pindolol / Q000031:analogs & derivatives; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D014132:Trachea / Q000033:anatomy & histology / Q000378:metabolism*
D000319:Adrenergic beta-Antagonists; D007093:Imidazoles; D007457:Iodine Radioisotopes; D011943:Receptors, Adrenergic, beta; D020120:Iodocyanopindolol; D010869:Pindolol; C049763:CGP 20712A