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Characterization of propranolol‐resistant (−)‐[ 125 I]‐cyanopindolol binding sites in rat soleus muscle
Author(s) -
Roberts Susan J.,
Molenaar Peter,
Summers Roger J.
Publication year - 1993
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.1476-5381.1993.tb13576.x
Subject(s) - alprenolol , propranolol , pindolol , chemistry , agonist , binding site , stereochemistry , medicine , partial agonist , soleus muscle , affinities , endocrinology , receptor , biochemistry , skeletal muscle , biology
1 The characteristics of a propranolol‐resistant (−)‐[ 125 I]‐cyanopindolol (CYP) binding site in rat soleus muscle were determined. 2 Saturation studies performed on homogenates of rat soleus muscle showed two phases of (−)‐[ 125 I]‐CYP binding, a high affinity site ( K D1 30.5 ± 16.3 p m , B max 9.4 ± 1.38 fmol mg −1 protein) and a lower affinity site ( K D2 522.5 ± 29.1 p m , B max 62.19 ± 11.76 fmol mg −1 protein, n = 4). 3 In rat soleus muscle homogenates labelled with (−)‐[ 125 I]‐CYP (500 p m ), (−)‐propranolol competition curves were biphasic with p K D values of 8.30 ± 0.19, and 5.33 ± 0.08, n = 7. 4 Competition between (−)‐[ 125 I]‐CYP (500 p m ) and (±)‐tertatolol, (±)‐nadolol, (±)‐alprenolol, (±)‐CYP, and (−) and (+)‐pindolol showed that these compounds competed for binding at the propranolol‐resistant site with affinities lower than those displayed at typical β‐adrenoceptors. The atypical β‐adrenoceptor agonists BRL 37344, SR58611A and ICI D7114 and the partial agonist (±)‐CGP 12177 also competed for (−)‐[ 125 I]‐CYP binding. 5 Stereoselectivity was demonstrated for the stereoisomers of alprenolol and tertatolol. The (−)‐isomers of alprenolol and tertatolol had higher affinity than their corresponding (+)‐isomers (3.1 and 2.6 fold respectively). These low stereoselectivity values are a characteristic of atypical β‐adrenoceptors. 6 The β‐adrenoceptor agonists, (−)‐adrenaline, (−)‐isoprenaline and (−)‐noradrenaline, all showed lower affinity than the atypical β‐adrenoceptor agonists and competition curves appeared biphasic in nature. 7 These results confirm the presence of a propranolol‐resistant (−)‐[ 125 I]‐CYP binding site in rat soleus muscle. The affinities of the tested compounds at the propranolol‐resistant (−)‐[ 125 I]‐CYP binding site show similarities to their affinities at ‘atypical’ β‐adrenoceptors in adipocytes and gastrointestinal tissues and at the cloned β 3 ‐adrenoceptor.