MODULATION OF DOPAMINE RECEPTOR AGONIST BINDING-SITES BY CATIONS AND ESTRADIOL IN INTACT PITUITARY AND 7315A TUMORS

The effects of Na+, K+, Mg2+ and Ca2+ on the agonist binding sites of D2 dopamine (DA) receptors were studied in 7315a pituitary tumors. The agonist high and low affinity states of the D2 receptors were investigated with apomorphine competition for [H-3]spiperone binding at 25-degrees. In the tumor, all cations markedly increased the affinity of the high affinity binding site, while the affinity of the low affinity binding site was increased only by Na+. The proportion of high to low affinity states was not affected significantly by K+ and Ca2+, whereas it was decreased by Na+ and increased by Mg2+; none of these cations affected the total density of the D2 receptors. The in vitro regulation of D2 receptors by 17-beta-estradiol (E2) was next studied in 7315a tumors and bovine intact adenohypophysis. In intact anterior pituitary, a partial conversion of the high to the low affinity state was obtained in the presence of GTP, while in tumoral pituitary, a complete conversion was observed. Addition of 1 nM E2 to the in vitro incubation mixture prevented these conversions and resulted in a partial return of the high affinity state of the D2 receptors to their control values in both normal and tumoral pituitary. In another experiment, using increasing concentrations of E2 (0.01 to 100 nM) and GTP (10(-8) to 10(-3) nM) on [H-3]n-propylnorapomorphine ([H-3]NPA) binding to the D2 receptors in bovine intact adenohypophysis, 1 and 10 nM E2 doubled the IC50 of GTP to decrease [H-3]NPA binding. The results show that agonist high and low affinity states of D2 receptors in 7315a tumors are regulated normally by cations. In addition, E2 inhibited the effect of GTP on the agonist sites of the D2 receptors in both intact anterior pituitary tissue and 7315a tumors.