Distinction between Two Subpopulations of β1‐Adrenergic Receptors in Human Adipose Cells

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Abstract
The .beta.-adrenergic receptors in human adipose membranes were identified by the specific and saturable binding of the .beta.-adrenergic antagonist (-)-[3H]dihydroalprenolol. The total number of sites in control membranes was 0.32 .+-. 0.03 pmol/mg protein and the Kd was 2.6 nM and 2.5 nM as determined by Scatchard analysis of experiments on equilibrium binding and kinetics, respectively. The .beta.1-adrenergic nature of the receptors was derived from the order of potencies of .beta.-adrenergic agonists (isoproterenol > norepinephrine > epinephrine) to compete with (-)-[3H]dihydroalprenolol for binding. Studies of saturation binding, kinetics and competition binding revealed the presence of a single class of .beta.1-adrenergic receptors. Prolonged incubation of human adipose cells in the presence of (-)-norepinephrine decreases the lipolytic response to .beta.-adrenergic agonists and reduces by 50% the concentration of .beta.-adrenergic receptors. Kd values for (-)-[3H]dihydroalprenolol and the .beta.-adrenergic agonists remain unchanged. Catecholamines produce a rapid conformational change of .apprx. 50% of the receptors in control membranes as revealed by their increased sensitivity towards inactivation by the alkylating agent N-ethylmaleimide. This inactivation process is not observed in desensitized membranes, indicating that desensitization and inactivation by agonists plus N-ethylmaleimide affect the same receptor population. The .beta.1-adrenergic receptors in human adipocytes can be divided into 2 subpopulations on the basis of the different consequences of their interaction with agonist molecules.