Ligand binding profiles of δ-opioid receptor in human cerebral cortex membranes: Evidence of δ-opioid receptor heterogeneity

In this study, receptor binding profiles of opioid ligands for subtypes of opioid δ-receptors were examined employing [³H]D-Pen²,D-Pen⁵-enkephalin ([³H]DPDPE) and [³H]Ile^5,6-deltorphin II ([³H]Ile-Delt II) in human cerebral cortex membranes. [³H]DPDPE, a representative ligand for δ₁ sites, labeled a single population of binding sites with apparent affinity constant (Kd) of 2.72 ± 0.21 nM and maximal binding capacity (Bmax) value of 20.78 ± 3.13 fmol/mg protein. Homologous competition curve of [³H]Ile-Delt II, a representative ligand for δ₂ sites, was best fit by the one-site model (Kd = 0.82 ± 0.07 nM). Bmax value (43.65 ± 2.41 fmol/mg) for [³H]Ile-Delt II was significantly greater than that for [³H]DPDPE. DPDPE, [D-Ala²,D-Leu⁵]enkephalin (DADLE) and 7-benzylidenaltrexone (BNTX) were more potent in competing for the binding sites of [³H]DPDPE than for those of [³H]Ile-Delt II. On the other hand, deltorphin II (Delt II), [D-Ser²,Leu⁵,Thr⁶]enkephalin (DSLET), naltriben (NTB) and naltrindole (NTI) were found to be equipotent in competing for [³H]DPDPE and [³H]Ile-Delt II binding sites. These results indicate that both subtypes of opioid δ-receptors, δ₁ and δ₂, exist in human cerebral cortex with different ligand binding profiles.