SYNTHESIS AND BINDING CHARACTERISTICS OF TRITIATED TIPP[PSI], A HIGHLY SPECIFIC AND STABLE DELTA-OPIOID ANTAGONIST

The pseudopeptide H-Tyr-Tic Psi[CH2-NH]Phe-Phe-OH (TIPP[Psi]) is a del ta opioid antagonist with high delta receptor affinity and unprecedent ed delta selectivity. TIPP[Psi] was radiolabelled by catalytic tritiat ion of its precursor [Tyr(3',5'I-2)(1)]TIPP[Psi]. The resulting radiol igand, [H-3]TIPP[Psi], had a specific activity of 1.77 TBq/mmol (47.9 Ci/mmol) and showed high stability against enzymatic degradation. [H-3 ]TIPP[Psi] binding to rat brain membranes was saturable and Scatchard analysis indicated a single binding site with a K-d of 0.98 nM and a B -max of 105.4 fmol/mg. A study of [H-3]TIPP[Psi] binding displacement by various receptor-selective opioids showed the expected rank order o f potency (delta much greater than mu > kappa). [H-3]TIPP[Psi] represe nts an excellent new radioligand for delta receptor labelling studies in vitro and in vivo.