Autoradiographic localization of β‐adrenoceptors in pig lung using [125I]‐iodocyanopindolol

Abstract

The binding of the β‐adrenoceptor radioligand [125I]‐iodocyanopindolol (I‐CYP) has been studied in pig lung parenchyma and the distribution of binding sites visualised by light microscopic autoradiography. I‐CYP binding was saturable (maximum binding capacity Bmax = 51 ± 3 fmol mg−1 protein), involving sites with high affinity (dissociation constant KD = 73 ± 10 pM). Specific I‐CYP binding was displaceable both by β‐adrenoceptor agonists ((−)‐isoprenaline > (−)‐adrenaline > (±)‐fenoterol > (−)‐noradrenaline > (+)‐isoprenaline > (±)‐RO363) and antagonists ((±)‐propranolol > ICI‐118551 > atenolol), indicating a predominance of β2‐adrenoceptors. Further analysis showed that displacement data for the β1‐selective antagonist atenolol and the β2‐selective antagonist ICI‐118551 were fitted best to a 2 binding site model and that both β1‐ and β2‐adrenoceptors were present in pig lung in the ratio 28:72 respectively. Autoradiographic grains were localized over tissue and were most dense over alveolar walls > vascular endothelium > vascular smooth muscle > bronchial smooth muscle = bronchial epithelium. Atenolol (10−5 M) caused a 31 % reduction in specific grain density over alveolar wall tissue, while a 10 fold lower concentration of ICI‐118551 (10−6 M) caused a 50% decrease. These results are consistent with binding data in pig lung parenchyma demonstrating a mixed population of β‐adrenoceptors with a predominance of the β2 subtype. Approximately 95 % of the parenchymal β‐adrenoceptors were associated with the alveolar wall as a mixed population of the β1 and β2 subtypes in the ratio 30:70 respectively. A greater proportion of the β‐adrenoceptors associated with bronchial and vascular smooth muscle seemed to be of the β2 subtype. It is possible that the previously described relaxant responses of the pig lung parenchyma strip to β‐agonists, mediated via β2‐adrenoceptors, resulted from the sum of reactivities in airway and vascular smooth muscle together with relaxation of alveolar interstitial cells. 1986 British Pharmacological Society