Comparative binding properties of linear and cyclic δ‐selective enkephalin analogues: [3H]‐[D‐Thr2, Leu5] enkephalyl‐Thr6 and [3H]‐[D‐Pen2, D‐Pen5] enkephalin

Abstract

The range of δ‐selectivity of linear and cyclic analogues of enkephalin in rat brain was found to be: [D‐Pn⁵] enkephalin (DPLPE) > [D‐Pn⁵] enkephalin (DPDPE) > [D‐Thr², Leu⁵] enkephalyl‐Thr⁶ (DTLET) > [D‐Ser², Leu⁵] enkephalyl‐Thr⁶ (DSLET). Saturation experiments performed with [³H]DPDPE and [³H]DTLET in NG108‐15 cells and rat brain showed similar binding capacities for both the ligands, but the δ‐affinity of [³H]DTLET (K _D ≈ 1.2 nM) was much better than that of [³H]DPDPE (K _D ≈ 7.2 nM). The rather low δ‐affinity of DPDPE induced high experimental errors cancelling the benefit of its better δ‐selectivity. Binding experiments in rat or guinea‐pig brains showed, in both cases, the better δ‐selectivity of [³h]dtlet compared to [³h]slet. The former peptide remains at this time the most appropriate radioactive probe for binding studies of δ‐receptor.