Influence of sodium and sulphydryl groups on [3H]sulpiride binding sites in rat striatal membranes.
The effect of thiol reagents on the specific binding of the atypical neuroleptic, sulpiride, to rat striatal membranes are 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 to alkylation.
D000818:Animals; D001665:Binding Sites; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004229:Dithiothreitol / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D005033:Ethylmaleimide / Q000494:pharmacology; D006150:Guanine Nucleotides / Q000494:pharmacology; D051381:Rats; D012964:Sodium / Q000494:pharmacology*; D013439:Sulfhydryl Reagents / Q000494:pharmacology*; D013469:Sulpiride / Q000378:metabolism*
D006150:Guanine Nucleotides; D013439:Sulfhydryl Reagents; D013469:Sulpiride; D012964:Sodium; D005033:Ethylmaleimide; D004229:Dithiothreitol; D004298:Dopamine