LY164929: a highly selective ligand for the lower affinity [3H]D-Ala2-D-Leu-5-enkephalin binding site

Most radiolabeled ligands used to label opiate receptors bind to multiple binding sites. Subtype-selective ligands make possible the labeling of single sites by virtue of their ability to "block" binding of the radiolabeled ligand to selected subtypes. This study compares the selectivity of several ligands for the higher and lower affinity [3H]D-Ala2-D-Leu-5-enkephalin binding sites. The results demonstrated that while morphine and D-ala2-MePhe4,Gly-ol5-enkephalin were 80- and 256-fold selective for the lower affinity [3H]D-Ala2-D-Leu-5-enkephalin binding site, LY164929 was 1,986-fold selective. Additional experiments indicated that whereas morphine was a noncompetitive inhibitor at the lower affinity [3H]D-Ala2-D-Leu-5-enkephalin binding site, LY164929 was a competitive inhibitor, suggesting that this peptide might exhibit different properties in vivo than other mu-like ligands.