Heterogenous Binding of 3H‐Remoxipride to Membranes of Rat Liver and Brain

Abstract

The binding of the antipsychotic agent 3H-remoxipride to membranes of rat liver and brain (whole brain and cerebellum) was studied with filtration technique. Saturable high affinity binding was obtained for all three types of tissue preparations. Heterogenous binding sites were found since various types of compounds inhibited the binding of 3H-remoxipride with shallow dose-response curves. In the liver preparation it was possible to differentiate between two different binding sites. One site, called rem1, was defined with 100 nM alaproclate and bound sigma 2 ligands with high affinity, e.g. haloperidol, GBR 12909, DTG and (+)-3-PPP. High correlation (r = 0.93) was obtained between the inhibition of the binding of 3H-remoxipride to the rem1 site and the inhibition of the binding of the sigma ligand 3H-DTG reported previously (Ross 1991), indicating that the rem1 site is identical to a sigma 2-like binding site. The other 3H-remoxipride binding site in the rat liver, rem2 appears to be identical to the site binding alaproclate, proadifen and cocaine with high affinity. Cd2+ and Zn2+ were potent inhibitors of both binding sites, Cd2+ particularly of rem2 binding and Zn2+ preferably of rem1 binding. The apparent Bmax (pmol/g original tissue) and KD (nM) values for rem1 binding were 441 +/- 43 and 80 +/- 14, and for rem2 binding 727 +/- 116 and 95 +/- 6. The binding of 3H-remoxipride to the brain preparations was also inhibited with shallow dose-response curves.(ABSTRACT TRUNCATED AT 250 WORDS)