Reversible inhibition of specific 3H-spiroperidol binding by heavy metal ions in rat striatum

Four divalent heavy metals interact with neural membranes from rat striatum in vitro to inhibit ligand binding of dopamine receptors as labelled by ³H-spiroperidol, a dopamine antagonist. Their relative inhibitory potencies in decreasing order are as follows: copper > lead > cadmium > mercury. Copper exhibited an IC50 value of 6.7 x 10^-6 M is the most potent in competing with 2.5 x 10^-8 M ³H-spiroperidol for receptor binding. Equilibrium binding constants computed from Scatchard analysis of results show that copper reduces the density as well as the affinity of the receptors in binding the ligand. Partial reactivation of dopamine receptors from copper inhibition is achieved by adding the chelating agent d-penicillamine, but not diethylenetriaminepentaacetic acid (DTPA). The relevance of these findings is discussed in relation to the clinical symptoms of Wilson's disease and abnormal copper accumulation in basal ganglia secondary to chronic liver disease.