Effect of transition or heavy metals on [3H]haloperidol binding in rat striatal membranes in vitro.

Our previous experiments have shown that several metal cations affect dopaminergic uptake and release processes in synaptosomes in vitro. It is thus possible that other membrane-related steps of neurotransmission, such as receptor binding, are affected as well. We studied the effect of Mn2+, Cu2+, Cd2+, Zn2+, Hg2+, Pb2+ and of two organometals, methyl mercury and triethyl lead, on [3H]haloperidol binding in the striatal P2 fraction assuming that such a study would reveal direct effects of the ions on dopaminergic D2 receptor binding. According to non-linear curve fitting and Scatchard analysis, [3H]haloperidol bound to two sites in striatal tissue. The Kd of the higher affinity site was 0.14 +/- 0.05 nM and the Bmax 226.3 +/- 50.3 fmol/mg protein. The respective values for the lower affinity site were 2.49 +/- 0.56 nM and 678.3 +/- 111.4 fmol/mg protein. Among the divalent cations, Hg2+ (IC50 0.7 microM) and Cu2+ (IC50 2.9 microM) inhibited the high affinity [3H]haloperidol binding most potently. The inhibition by Cu2+ was due to a decrease in the binding affinity (increase in the Kd) while the number of binding sites remained unchanged. Zn2+ inhibited the binding by 41.8% and Cd2+ by 38.7% at 10 microM concentration while Pb2+ and Mn2+ did not affect binding significantly at this or lower concentrations. Methyl mercury (IC50 0.9 microM) and triethyl lead (IC50 2.6 microM) inhibited binding as well. Both these organometallic cations decreased the binding affinity but did not change significantly the number of binding sites.(ABSTRACT TRUNCATED AT 250 WORDS)