Cation specificity of 3H-sulpiride binding involves alteration in the number of striatal binding sites

Specific 3H-sulpiride binding to rat striatal membranes shows an absolute requirement for the presence of sodium ions in the incubation buffer. Potassium, rubidium and caesium ions were unable to initiate specific 3H-sulpiride binding in a sodium free buffer, and lithium ions could only partially replace sodium ions. Specific 3H-spiperone binding was unaffected by variation of the cation content of the incubation buffer. The alteration in 3H-sulpiride binding caused by sodium and lithium ions was due predominantly to an increase in the number of available binding sites, rather than to altered receptor affinity. Sodium ions may be essential for the accessability of 3H-sulpiride to a single site labelled also by 3H-spiperone. However, the Ki value for sulpiride displacement of 3H-spiperone in the presence of sodium ions was 20 times greater than the KD value for 3H-sulpiride binding. So, 3H-sulpiride may interact with a highly sodium dependent binding site distinct from that labelled by 3H-spiperone.