SYNTHESIS AND BINDING CHARACTERISTICS OF THE HIGHLY SPECIFIC, TRITIATED DELTA-OPIOID ANTAGONIST [H-3] 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 b rain membrane binding sites with a K(d) value of 0.64 nM and a B(max) of 82 fmol/mg protein. Binding competition experiments with various un labelled 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 d elta selectivity and low non-specific binding, [H-3]TIPP represents an excellent new radioligand for the study of delta opioid receptor inte ractions.