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

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