High number of high-affinity binding sites for (-)-[3H]dihydroalprenolol on isolated hamster brown-fat cells. A study of the beta-adrenergic receptors.
The beta-adrenergic receptors of hamster brown adipocytes have been characterised by binding of the radioactive ligand (-)-[3H]dihydroalprenolol, directly to isolated intact cells in suspension. The brown fat cell contains 57,000 specific and saturable binding sites which have a dissociation constant (Kd) for [3H]dihydroalprenolol of 1.4 nM as determined by Scatchard analysis. The kinetically derived Kd, determined from forward and reverse rate constants, is 5 nM. Both of these values are in agreement with the dissociation constant (Kd = 2.2 nM) for alprenolol, determined from competition studies with [3H]dihydroalprenolol in these cells. Beta-adrenergic agonists competed for the specific binding sites with a typical beta 1-adrenergic specificity. The order of potency of agonists agrees well with the ability of these agents to stimulate respiration in isolated brown adipocytes: 50% stimulation of respiration occurs with apparently less than 10% occupancy of binding sites. Both the high affinity and high number of specific binding sites of [3H]dihydroalprenolol in brown fat cells presumably reflect the generally accepted dominating role of catecholamines in the regulation of brown fat metabolism and non-shivering thermogenesis.
D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000526:Alprenolol / Q000031:analogs & derivatives*; D000818:Animals; D006224:Cricetinae; D004082:Dihydroalprenolol / Q000494:pharmacology*; D007700:Kinetics; D008647:Mesocricetus / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D013565:Sympatholytics / Q000494:pharmacology; D013566:Sympathomimetics / Q000494:pharmacology
D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D013565:Sympatholytics; D013566:Sympathomimetics; D004082:Dihydroalprenolol; D000526:Alprenolol