Comparison of the pharmacological profiles of adrenergic drugs (including BRL-agonists) at [3H]prazosin and [3H]CGP-12177 binding sites in brown adipose tissue.
1. In order to determine the selectivity of classical and novel adrenergic agents for alpha 1- and beta-adrenergic receptors in brown adipose tissue, the ability of these agents to compete for binding sites labelled with [3H]prazosin and [3H]CGP-12177, respectively, was investigated. 2. The beta-antagonist propranolol, known to inhibit norepinephrine-induced respiration in micromolar concentrations, bound to the [3H]CGP-12177 site with nanomolar affinity. 3. Among agonists, only isoprenaline showed high selectivity for beta-receptors, and only oxymetazoline for alpha 1-receptors. 4. Unexpectedly, the novel thermogenic agonists (BRL-agonists), shown to be potent and selective stimulators of brown fat thermogenesis, were unselective and bound only with low affinity to the [3H]CGP-12177 binding sites. 5. These results suggest that the beta-adrenergic binding site in brown adipose tissue identified here with [3H]CGP-12177 may not be the one (or not the only one) coupled to thermogenesis.
Mohell
N
N
Wenner-Gren Institute, University of Stockholm, Sweden.
Nedergaard
J
J
D002001:Adipose Tissue, Brown / Q000187:drug effects* / Q000378:metabolism; D000319:Adrenergic beta-Antagonists; D000818:Animals; D006224:Cricetinae; D066298:In Vitro Techniques; D008566:Membranes / Q000187:drug effects; D008647:Mesocricetus; D011224:Prazosin; D011412:Propanolamines; D011869:Radioligand Assay; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D013566:Sympathomimetics / Q000494:pharmacology*
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D013566:Sympathomimetics; C033394:CGP 12177; D011224:Prazosin