A differential interaction of putative ?-selective agonists with opiate binding sites in rat brain

The availability of tritium-labelled sufentanil ([(3)H]SUF) allowed for a further radioligand analysis of opiate binding sites in rat brain. A comparison of the binding characteristics of [(3)H]SUF and [(3)H]dihydromorphine ([(3)H]DHM) revealed a very similar potency in their mutual displacement by unlabelled analogues. Furthermore, a series of putative ?-opiate agonists displayed equal potencies in displacing either [(3)H]SUF and [(3)H]DHM, the only striking exception being the highly ?-selective opioid peptide morphiceptin which was 33 times less potent in inhibiting [(3)H]SUF as compared to [(3)H]DHM binding. Additional experiments revealed further pronounced differences in [(3)H]SUF and [(3)H]DHM binding characteristics: the total amount of binding sites for [(3)H]SUF was 4 times higher than that for [(3)H]DHM and the regional distribution within particular brain areas displayed considerable differences. Furthermore, the binding of [(3)H]SUF was differentially modulated by sodium and GTP as compared to [(3)H]DHM binding. These data suggest that in rat brain, [(3)H]SUF interacts both with ?-opiate sites recognizing [(3)H]DHM and another type of opiate site, which cannot be equated with any of the, as yet, described ?- or ?-binding sites, and rather, represents a subclass of ?-opiate receptor sites. These experiments, thus, support the notion of subclasses (isoreceptors) for different types of opiate receptors.