Following the description of (3H]Ile5,6,deltorphin II, when it was reported that changes in hydrophobicity at positions 5 and 6 give rise to analogues with increased δ-receptor affinity and selectivity, new conformationally restricted deltorphin analogues were designed. A synthetic amino acid, 2-aminotetralin-2-carboxylic acid (Atc), was introduced at position 3 instead of Phe in IIe5,6deltorphin I and II, and the resultant compounds were prepared in tritiated form. Opioid binding sites specific for [3H]s-Atc3,Ile5,6deltorphin I and [3H]R-Atc3,Ile5,6deltorphin II were characterized in rat brain membranes. Their binding was saturable, stereoselective and inhibited by δ-selective ligands with high potency. They labelled single class of opioid sites at 35°C with high affinity (K(d) - 0.3 nM), B(max) values of 130 fmo/mg protein, and vary low non-specific binding was observed. Both tritiated deltorphin analogues showed δ-receptor specificity in rat brain, therefore they could represent excellent new radioligands for investigating the complexity of the opioid receptor systems.
ASJC Scopus subject areas
- Endocrine and Autonomic Systems
- Cellular and Molecular Neuroscience