3H-(-)DO 710 discriminates guanine nucleotide sensitive and insensitive dopamine binding sites

Abstract

(-)DO 710, a substituted benzamide derivative which discriminates dopamine D-2 and D-4 binding sites (Sokoloff et al. 1984), and antagonises in a differential manner several apomorphine-induced behavioral responses (Schwartz et al. 1984) was tritiated and used namely to differentially label the D-4 site. In striatum the 3H-(-)DO 710 saturation curve was best explained by the presence of two classes of sites with a 7-fold difference in affinity (Kd values of 3.0 nM and 0.42 nM) and Bmax values of 316 and 106 fmol X mg protein-1, respectively which correspond to the D-2 and D-4 sites (Sokoloff et al. 1984). In spite of its limited selectivity, 3H-(-)DO 710 in low concentration (0.2 nM) could be used to preferentially label striatal D-4 site as shown by the inhibition potencies of discriminant benzamide derivatives (DBD), significantly higher than at pituitary D-2 site (receptor) whereas classical neuroleptics including metoclopramide were equally potent at both sites. The affinity of a variety of agonists for striatal sites labeled with 0.2 nM 3H-(-)DO 710 generally differed from their affinity for the two states of the pituitary D-2 receptor (with high and low affinity for agonists, respectively); compounds like lisuride, N-propylnorapomorphine or pergolide had very high affinity for the striatal 3H-(-)DO 710 site. In pituitary from oestradiol-treated rats, where only D-2 site occurs, only the low-affinity site for 3H-(-)DO 710 (Kd = 2.8 nM) was found.(ABSTRACT TRUNCATED AT 250 WORDS)