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Autoradiographic localization of β‐adrenoceptors in pig lung using [ 125 I]‐iodocyanopindolol
Author(s) -
Goldie R.G.,
Papadimitriou J.M.,
Paterson J.W.,
Rigby P.J.,
Spina D.
Publication year - 1986
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.1476-5381.1986.tb10243.x
Subject(s) - iodocyanopindolol , atenolol , propranolol , endocrinology , medicine , dissociation constant , population , chemistry , isoprenaline , fenoterol , radioligand , antagonist , lung , binding site , receptor , agonist , biology , biochemistry , intrinsic activity , stimulation , environmental health , asthma , blood pressure
1 The binding of the β‐adrenoceptor radioligand [ 125 I]‐iodocyanopindolol (I‐CYP) has been studied in pig lung parenchyma and the distribution of binding sites visualised by light microscopic autoradiography. 2 I‐CYP binding was saturable (maximum binding capacity B max = 51 ± 3 fmol mg −1 protein), involving sites with high affinity (dissociation constant K D = 73 ± 10 pM). 3 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 β 2 ‐adrenoceptors. Further analysis showed that displacement data for the β 1 ‐selective antagonist atenolol and the β 2 ‐selective antagonist ICI‐118551 were fitted best to a 2 binding site model and that both β 1 ‐ and β 2 ‐adrenoceptors were present in pig lung in the ratio 28:72 respectively. 4 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 β 2 subtype. 5 Approximately 95 % of the parenchymal β‐adrenoceptors were associated with the alveolar wall as a mixed population of the β 1 and β 2 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 β 2 subtype. 6 It is possible that the previously described relaxant responses of the pig lung parenchyma strip to β‐agonists, mediated via β 2 ‐adrenoceptors, resulted from the sum of reactivities in airway and vascular smooth muscle together with relaxation of alveolar interstitial cells.