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RELATIONSHIP BETWEEN THE (−)‐[ 3 H]‐DIHYDROALPRENOLOL BINDING TO β‐ADRENOCEPTORS AND TRANSMEMBRANE 86 Rb EFFLUX OF THE BC 3 H1 NONFUSING MUSCLE CELL LINE
Author(s) -
MAUGER JEANPIERRE,
WORCEL MANUEL
Publication year - 1980
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.1476-5381.1980.tb10866.x
Subject(s) - alprenolol , chemistry , dihydroalprenolol , dissociation constant , propranolol , practolol , binding site , stereochemistry , receptor , antagonist , endocrinology , biochemistry , partial agonist , biology
1 We have studied the binding properties of the β‐adrenoceptor antagonist [ 3 H]‐dihydroalprenolol ([ 3 H]‐DHA) on a membrane preparation of the non‐fusing muscle cells BC 3 H1. 2 [ 3 H]‐DHA appears to bind to two classes of sites. The first site has a high affinity ( K D = 0.53 n m ) and a low capacity ( B max = 58 fmol/mg of protein). The second site has a low affinity ( K D =110 n m ) and a high capacity ( B max = 1100 fmol/mg of protein). 3 The pharmacological properties of the high affinity low capacity site correspond to the known properties of the β 2 ‐adrenoceptors since the agonists inhibit [ 3 H]‐DHA binding following the series isoprenaline > adrenaline > noradrenaline > phenylephrine and the antagonists following the series alprenolol ≃ propranolol > butoxamine > practolol > phentolamine. 4 The binding properties of the β‐adrenoceptors were correlated with the effect of β‐adrenoceptor agonists and antagonists on 86 Rb efflux rate from BC 3 H1 cells. 5 There is very good correlation between the dissociation constants obtained by inhibition of [ 3 H]‐DHA binding by the antagonists alprenolol and propranolol, and the inhibition constants calculated from their antagonism of the 86 Rb efflux rate stimulation by adrenaline. The ratio of the dissociation constants obtained by inhibition of [ 3 H]‐DHA binding by agonists and their EC 50 , calculated from 86 Rb efflux curves, is higher than 1. This high K D /EC 50 ratio indicates a high coupling efficiency between receptor occupancy by agonists and the biological effect measured.