Influence of Sodium and Sulphydryl Groups on [3H]Sulpiride Binding Sites in Rat Striatal Membranes

Abstract: The effect of thiol reagents on the specific binding of the atypical neuroleptic, sulpiride, to rat striatal membranes was examined. Pretreatment of membranes with N -ethylmaleimide (NEM), but not with iodoacetamide or dithiothreitol (DTT), diminishes [³H]sulpiride binding. The effect is dependent on time, temperature, and the concentration of NEM. The reaction proceeds with pseudo-first-order rate kinetics, indicating the involvement of a single essential SH group in the binding of [³H]sulpiride to striatal membranes sites. Both sodium and sulpiride, but not nucleotides, protect the [³H]sulpiride sites from NEM inactivation in a dose-dependent fashion. As sodium is essential for [³H]sulpiride binding it is possible that in the presence of sodium and sulpiride a conformational change takes place that makes the essential SH group less accessible t o alkylation.