RELATIONSHIP BETWEEN INHIBITION OF CYCLIC-AMP PRODUCTION IN CHINESE-HAMSTER OVARY CELLS EXPRESSING THE RAT D-2(444) RECEPTOR AND ANTAGONIST AGONIST BINDING RATIOS

1 Radioligand binding assays using [H-3]-(-)-sulpiride, in the presence of 1 mM ethylenediaminetetraacetic acid (EDTA) and 100 mu M guanylylimidodiphosphate (GppNHp) and [H-3]-N0437 were developed to label the low and high agonist affinity states of the rD(2(444)) receptor (long form of the rat D-2 receptor) respectively. The ratios of the affinities of compounds in these two assays (K-app [H-3]-(-)-supiride/K-app [H-3]-N-0437) were then calculated. 2 The prediction that the binding ratio reflected the functional efficacy of a compound was supported by measurement of the ability of a number of compounds acting at dopamine receptors to inhibit rD(2(444))-mediated inhibition of cyclic AMP production. When the rank order of the ratios of a number of these compounds was compared to their ability to inhibit the production of cyclic AMP, a significant correlation was seen (Spearman rank correlation coefficient=0.943, P=0.01). 3 In conclusion, the sulpiride/N-0437 binding ratio reliably predicted the efficacy of compounds acting at dopamine receptors to inhibit cyclic AMP production mediated by the rD(2(444)) receptor.