tyrosyl-1-2-3-4-tetrahydro-3-isoquinolinecarbonyl-phenylalanyl-phenylalanine and Brain-Neoplasms

The binding properties and pharmacological activities of H-Tyr(3'-I)-Tic-Phe-Phe-OH ([Tyr(3'-I)1]TIPP) were studied. Similar to the delta-opioid receptor antagonist H-Tyr-Tic-Phe-Phe-OH (TIPP), [Tyr(3'-I)1]TIPP is a selective and potent ligand at delta-opioid receptors. The displacement curve of [3H]diprenorphine binding by [Tyr(3'-I)1]TIPP was shifted to the right in the presence of Na+ and 5'-guanylylimidodiphosphate, suggesting that it acted as a delta-opioid receptor agonist. [Tyr(3'-I)1]TIPP also behaved as a full agonist in the mouse vas deferens assay and its effect was both naloxone- and TIPP-reversible. These data show that monoiodination at the 3'-position of the N-terminal tyrosine aromatic ring of TIPP converted it from a potent and selective antagonist to a full agonist at delta-opioid receptors.

Topics: Amino Acid Sequence; Analgesics; Animals; Brain Neoplasms; Chromatography, High Pressure Liquid; Chromatography, Thin Layer; Enkephalin, D-Penicillamine (2,5)-; Enkephalins; Humans; Iodine; Mice; Molecular Sequence Data; Molecular Weight; Narcotic Antagonists; Neuroblastoma; Oligopeptides; Receptors, Opioid, delta; Spectrometry, Mass, Fast Atom Bombardment; Tetrahydroisoquinolines; Tumor Cells, Cultured; Tyrosine