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Ligand binding properties of putative β 3 ‐adrenoceptors compared in brown adipose tissue and in skeletal muscle membranes
Author(s) -
Sillence Martin N.,
Moore Nikki G.,
Pegg Graham G.,
Lindsay Derek B.
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.tb13743.x
Subject(s) - iodocyanopindolol , population , radioligand , medicine , propranolol , brown adipose tissue , endocrinology , ligand (biochemistry) , adipose tissue , pindolol , receptor , beta (programming language) , biology , skeletal muscle , antagonist , adrenergic receptor , chemistry , intrinsic activity , biochemistry , agonist , environmental health , computer science , programming language
1 The β‐adrenoceptor population was characterized in membrane preparations from rat brown adipose tissue (BAT) and from soleus muscle by use of the radioligand [ 125 I]‐iodocyanopindolol ([ 125 I]‐ICYP). In addition, atypical binding sites for [ 125 I]‐ICYP found in both tissues were examined, and the relationship between these sites and the putative rat β 3 ‐adrenoceptor is discussed. 2 It was established that BAT membranes host a mixed population of β 1 ‐ and β 2 ‐adrenoceptors. Of these two sites, 55% showed a high affinity for the β 1 ‐selective ligand CGP 20712A (p K 8.5), and 45% showed a high affinity for the β 2 ‐selective antagonist ICI 118551 (p K 8.6). Soleus muscle membranes were found to host a population of β 2 ‐adrenoceptors, characterized by a high affinity for ICI 118551 (p K 9.1), but β 1 ‐adrenoceptors could not be detected in this preparation. 5‐Hydroxytryptamine receptors were not detected in either preparation. 3 In addition to β 1 ‐ and β 2 ‐adrenoceptors, atypical binding sites were identified in both tissues using high concentrations of radioligand (0.5–0.6 n m ) and in the presence of 1 μ m (−)‐propranolol. The atypical sites were abundant, representing 80 and 81% of the total [ 125 I]‐ICYP binding sites in BAT and soleus muscle respectively. When the p K values for 11 ligands were compared, the correlation coefficient for atypical sites in BAT and soleus muscle was 0.94. 4 The atypical binding sites showed a moderate affinity for (±)‐cyanopindolol (p K 7.3–7.7), poor stereoselectivity for the (+)‐ and (−)‐enantiomers of alprenolol (<10 fold), and a low affinity for β‐adrenoceptor antagonists and partial agonists in the order: (±)‐cyanopindolol>(−)‐alprenolol> (−)‐propranolol = (±)‐ICI 118551 >>(±)‐CGP20712A. The affinity of these ligands for the atypical sites reflects their behaviour in functional studies of putative β 3 ‐adrenoceptors in rat BAT, white adipose tissue, intestine and colon. 5 The atypical sites labelled by [ 125 I]‐ICYP were resistant to agonist binding, and while the order of affinity of the agonists BRL 37344 > isoprenaline > noradrenaline matches their order of potency at putative β 3 ‐adrenoceptors, none of these compounds caused displacement of the radioligand at concentrations below 10 μ m . 6 It is concluded that the atypical binding sites for [ 125 I]‐ICYP found in rat BAT and soleus muscle membranes are the same, and that these sites show some relationship to the putative rat β 3 ‐adrenoceptor identified in functional studies using antagonists. However, under the conditions used in the present study, p K values obtained for β 3 ‐agonist binding are not useful.