β‐Adrenergic Receptors and Catecholamine‐Sensitive Adenylate Cyclase in Rat Fat‐Cell Membranes: Influence of Growth, Cell Size and Aging

The influence of age and cell size on adipocyte β‐adrenergic receptors was studied using the binding of (−)‐[ 3 H]dihydroalprenolol to crude adipocyte membranes from rats of different ages (1–30 months). Age and cell size failed to modify the kinetics, the reversibility and the stereospecificity of (−)‐[ 3 H]dihydroalprenolol binding. Scatchard plots of the binding data obtained with membranes from young, adult and senescent rats showed the existence of binding sites with high affinity for (−)‐dihydroalprenolol and which have the characteristics of the β‐adrenergic receptors. The dissociation constant K d of these sites was not affected by age (15.1–20.5 nM), suggesting that the receptor properties do not change during aging or fat cell enlargement. In contrast, the apparent maximal number of β‐receptors varied with age and cell size: during completion of maturation (1–8 months), it increased proportionally to the fat cell surface, reaching at maturity the value of 40800 receptors per cell. With senescence (12–30 months), on the contrary, although cell size remained constant over this period, the number of β‐receptors markedly declined, falling to 7200 receptors per cell in membranes from 30‐month‐old rats. These modifications were accompanied by parallel variations in the sensitivity of adenylate cyclase to catecholamines, but not to fluoride, suggesting that the catecholamine receptors and the adenylate cyclase catalytic sites develop independently. In contrast, the lipolytic responsiveness of adipocytes to catecholamines started to decline already during completion of maturation, an effect which seems thus to result from an action of age on one or more of the lipolytic steps localized beyond the catecholamine receptor‐adenylate cyclase system.