Adrenoceptor occupancy in isolated human fat cells and its relationship with lipolysis rate.

The relationship between lipolysis and adrenoceptor occupancy was determined in isolated human fat cells, which possess both lipolytic beta-adrenoceptors and antilipolytic alpha 2-adrenoceptors. The beta-adrenoceptor agonist, isoprenaline, and the alpha 2-adrenoceptor agonist, clonidine, had lower affinities to compete with antagonist radioligands (Ki) than to affect the rate of lipolysis (Ka). At 1 min of incubation human fat cells bound isoprenaline and clonidine with high affinity to beta- and alpha 2-adrenoceptors, respectively, but this high-affinity binding rapidly converted to a low-affinity state. The relationship between lipolysis and adrenoceptor occupancy was also assessed after long-lasting receptor inactivation. The inactivation of a small receptor fraction shifted the dose-response curves for isoprenaline and clonidine to the right but did not alter the maximum effect of the agonists (responsiveness). These results suggest that alpha 2- and beta-adrenoceptors are coupled to lipolysis according to similar models. There is a non-linear relationship between receptor and effector for both receptors, which can be explained by the co-existence of spare receptors and a transient high-affinity state of the receptors for agonists.