DIFFERENTIAL ANTAGONISM BY NALTRINDOLE-5'-ISOTHIOCYANATE ON [H-3] DSLET AND [H-3] DPDPE BINDING TO STRIATAL SLICES OF MICE

Naltrindole-5'-isothiocyanate (5'-NTII), a nonequilibrium delta opioid receptor antagonist, has been shown to antagonize differentially the antinociception induced by DSLET without affecting that induced by DPD PE. In the present study, we investigated whether or not 5'-NTII can d ifferentially affect DSLET and DPDPE binding to receptor sites in stri atal slices of mouse brain. We found that 5'-NTII only changed the bin ding characteristics of [H-3]DSLET and not that of [H-3]DPDPE. Saturat ion binding studies revealed that 5'-NTII treatment in vitro inhibited [H-3]DSLET binding by decreasing the affinity but not the number of b inding sites. This finding was supported by saturation studies with [H -3]DSLET in striatal slices from mice that were pretreated with 5'-NTI I (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 o f mice of [H-3]DSLET but not that of [H-3]DPDPE. The binding parameter s also suggest that 5'-NTII may not antagonize [H-3]DSLET binding by a lkylating at the receptor recognition site because the number of bindi ng 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 [H-3]DS LET and [H-3]DPDPE by 5'-NTII strongly support the postulated existenc e of delta opioid receptor subtypes.