Differential antagonism by naltrindole-5′-isothiocyanate on [³H]DSLET and [³H]DPDPE binding to striatal slices of mice

Naltrindole-5′-isothiocyanate (5′-NTII), a nonequilibrium δ opioid receptor antagoniist, has been shown to antagonize differentially the antinociception induced by DSLET without affecting that induced by DPDPE. In the present study, we investigated whether or not 5′-NTII can differentially affect DSLET and DPDPE binding to receptor sites in striatal slices of mouse brain. We found that 5′-NTII only changed the binding characteristics of [³H]DSLET andnot that of [³H]DPDPE. Saturation binding studies revealed that 5′-NTII treatment in vitro inhibited [³H]DSLET binding by decreasing the affinity but not the number of binding sites. This finding was supported by saturation studies with [³H]DSLET in striatal slices from mice that were pretreated with 5′-NTII (10 nmol, i.c.v. or 10 mg/kg, s.c.). Thus, the results suggest that 5′-NTII can antagonize differentially the binding to striatal slices of mice of [³H]DSLET but not that of [³H]DPDPE. The binding parameters also suggest that 5′-NTII may not antagonize [³H]DSLET binding by alkylating at the receptor recognition site because the number of binding sites did not decrease. 5′-NTII may bind to some other part of the membrane to indirectly desensitize the receptor to a low affinity form. Lastly, the differential alteration of binding sites between [³H]DSLET and [³H]DPDPE by 5′-NTII strongly support the postulated existence of δ opioid receptor subtypes.