Beta-adrenergic regulation of prostaglandin E2 receptors in human and rat adipocytes

Incubation of intact human and rat adipocytes with isoproterenol (10(-6) M) inhibits the specific binding of [3H] prostaglandin E2 (PGE2) by about 25% in human adipocytes and 50% in rat adipocytes. Scatchard analysis of [3H]PGE2 binding demonstrated that the isoproterenol-induced decrease in receptor activity may be due to a decrease in the apparent number of PGE2-binding sites, while the receptor affinity was unaltered. The inhibitory effect of isoproterenol on [3H]PGE2 binding was already seen after 10 min of isoproterenol treatment, and the maximal effect was obtained after 30-60 min. Half-maximal inhibition of binding occurred at a concentration of 5 X 10(-8) M isoproterenol. The effect of isoproterenol could be mimicked by epinephrine, theophylline, and (Bu)2-cAMP, indicating that elevated levels of cAMP are the common mechanism by which these agents affect PGE2 binding. Furthermore, the isoproterenol-induced inhibition of PGE2 binding was completely blocked by propranolol. The effects of some FFA and indomethacin were studied on PGE2 receptor binding, too. From the results of the latter studies, we suggest that endogeneously released arachidonic acid could account for some of the reduction in PGE2 binding. In conclusion, a beta-adrenergic receptor-mediated cAMP-dependent mechanism for the regulation of PGE2 receptor binding is demonstrated in both human and rat adipocytes.