Distribution of β₁‐ and β₂‐adrenoceptors in mouse trachea and lung: a quantitative autoradiographic study

Abstract

Binding and quantitative autoradiography were used to detect [125I]‐iodocyanopindolol (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 (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). 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 & Goldie, 1990), accounted for 69% of all β‐adrenoceptors in the airway smooth muscle.

ETB but not ETA receptor‐mediated contractions to endothelin‐1 attenuated by respiratory tract viral infection in mouse airways

“…Quantitative autoradiographic studies using ['251I]-endothelin-1 have previously revealed the existence of specific binding sites for ['251]-endothelin-1 in murine tracheal smooth muscle (Henry et al, 1990a). In the current study, competition binding experiments between ['251]-endothelin-1 and several recently developed ETA-receptor-selective (BQ-123) and ETB receptor-selective (sarafotoxin S6c, BQ3020) ligands have demonstrated that murine tracheal smooth muscle contains both ETA and ETB receptors in the ratio of 40%:60%, respectively.…”

Protective effect of endogenous β-adrenergic tone on lung fluid balance in acute bacterial pneumonia in mice

“…␤-Adrenoceptor stimulation may improve lung endothelial permeability (17,27,28) by inhibiting endothelial cell contraction and reducing intracellular gaps (19,34). In the mouse lung epithelia, ␤ 1 -and ␤ 2 -adrenoceptors coexist in the proportions of 18 and 82%, respectively (14). ␤ 2 -Adrenergic receptor stimulation reduces production of TNF-␣ and IL-6 in human macrophages (15) and suppresses lipopolysaccharide-induced lung inflammation (20,21).…”

Inhibitory effects of nordihydroguaiaretic acid on ETA‐receptor‐mediated contractions to endothelin‐1 in rat trachea

“…Autoradiographs of ['251]-ET-1 binding to rat tracheal sections were prepared as described previously (Henry et al, 1990b (Henry et al, 1990a). Four separate fields (3 over smooth muscle and one background measurement over a non-tissue area) were viewed from each tracheal section and quadruplicate total and non-specific slides were analysed.…”