Synthesis and binding characteristics of the highly specific, tritiated delta opioid antagonist [3H]TIPP

The recently discovered highly specific delta opioid antagonist H-Tyr-Tic-Phe-Phe-OH (TIPP) was radiolabelled by catalytic tritiation of its precursor [Tyr (3', 5'-I2)1]TIPP. The tritiated ligand labelled rat brain membrane binding sites with a Kd value of 0.64 nM and a Bmax of 82 fmol/mg protein. Binding competition experiments with various unlabelled mu-, delta- and kappa-opioid receptor ligands resulted in mu/delta and kappa/delta selectivity ratios of 600 and 9100, respectively, and thus confirmed the previously established high delta specificity of TIPP. Because of its high delta receptor affinity, extraordinary delta selectivity and low non-specific binding, [3H]TIPP represents an excellent new radioligand for the study of delta opioid receptor interactions.