Identification and subclassification of rat adipocyte beta-adrenoceptors using (+/-)-[125I]cyanopindolol

The ligand binding characteristics of beta-adrenoceptors on membranes derived from rat whole fat pads and isolated adipocytes have been compared to those present on lung membranes using the specific ligand (+/-)-[125I]cyanopindolol [(125I]CYP). The equilibrium dissociation constant (KD) of [125I]CYP was similar in all three preparations, whilst the degree of stereospecificity displayed by the isomers of propranolol varied between lung and isolated adipocyte membranes. The rank order of potency in displacing [125I]CYP binding was isoprenaline greater than adrenaline greater than noradrenaline in lung and whole fat pads, suggesting an overall beta 2-receptor subtype, and isoprenaline greater than noradrenaline greater than adrenaline in isolated adipocytes, suggesting a beta 1-receptor. Pharmacological characterisation of receptor subtype with selective beta-adrenoceptor agents indicated that all three preparations contained a heterogeneous receptor population (lung 80% beta 2, 20% beta 1; whole fat pad 62% beta 2, 38% beta 1; isolated adipocyte 15% beta 2, 85% beta 1). In view of the high proportion of beta 2-receptors on whole fat pad membranes, the overall amount of beta 2-receptors on isolated adipocytes may reflect contamination from other cell types. The nature of the beta 1-receptors present on fat cells is discussed in relation to the apparently atypical beta-receptor involved in mediating the functional lipolytic response.