Modulation of dopamine receptor agonist binding sites by cations and estradiol in intact pituitary and 7315a tumors

Abstract

The effects of Na +, K +, Mg 2+ and Ca 2+ on the agonist binding sites of D 2 dopamine (DA) receptors were studied in 7315a pituitary tumors. The agonist high and low affinity states of the D 2 receptors were investigated with apomorphine competition for [ 3H]spiperone binding at 25°. 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 Ca 2+, whereas it was decreased by Na + and increased by Mg 2+; none of these cations affected the total density of the D 2 receptors. The in vitro regulation of D 2; receptors by 17β-estradiol (E 2) 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 E 2 to the in vitro incubation mixture prevented these conversions and resulted in a partial return of the high affinity state of the D 2 receptors to their control values in both normal and tumoral pituitary. In another experiment, using increasing concentrations of E 2 (0.01 to 100 nM) and GTP (10 −8 to 10 −3 nM) on [ 3 H]n- propylnorapomorphine ([ 3H]NPA) binding to the D 2 receptors in bovine intact adenohypophysis, 1 and 10 nM E 2 doubled the ic 50 of GTP to decrease [ 3H]NPA binding. The results show that agonist high and low affinity states of D 2 receptors in 7315a tumors are regulated normally by cations. In addition, E 2 inhibited the effect of GTP on the agonist sites of the D 2 receptors in both intact anterior pituitary tissue and 7315a tumors.