Species variations in dopamine receptor binding

Binding of ³H-spiroperidol, ³H-apomorphine and ³H-ADTN (2-amino-6,7-dihydroxytetrahydronaphthalene) associated with dopamine receptors has been evaluated in corpus striatal membranes of calf, rat and human brains. Substantial species differences are apparent for numerous agonists and antagonists in competing for receptor binding. In general, dopamine receptor antagonists are more potent in rat and agonists more potent in calf. In competing for ³H-spiroperidol binding sulpiride, molindone and metaclopramide show the most pronounced species differences, being 3-10 times more potent in rat and human than in calf. In all three species agonists compete for ³H-spiroperidol binding with Hill coefficients less than one while antagonists inhibit ³H-spiroperidol binding with Hill coefficients of about 1.0. Conversely, ³H-apomorphine and ³H-ADTN binding in all three species is inhibited by antagonists with Hill coefficients less than 1.0 while agonists display Hill coefficients of about 1.0 In general agonists are more potent in competing for binding of ³H-apomorphine and ³H-ADTN than ³H-spiroperidol. However, a small component of dopamine, apomorphine and ADTN inhibition of ³H-spiroperidol binding displays very high affinity (IC₅₀ about 1 nM). In human amygdala ³H-spiroperidol appears to label serotonin receptors predominantly.