dynorphins and tyrosyl-prolyl-leucyl-glycinamide

Opioid properties of several morphiceptin- (Tyr-Pro-Phe-Pro-NH2), Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2) and dynorphin-derivatives were characterized in rat brain in vitro receptor binding assay and in electrically stimulated longitudinal muscle strip preparation of guinea pig ileum. In the case of morphiceptin-related peptides, an excellent correlation was found between the [3H]-naloxone binding displacement data and the agonist potencies determined in the bioassay. The "turning point' was the C-terminal amidation in the tri- and tetrapeptide pairs in both series. Tyr-MIF-1 derivatives showed weak affinity in the opioid receptor binding assay and none of them had any remarkable effect in the bioassay either as agonist or antagonist. The dynorphin A(1-10)-peptides modified at positions 5 and 8 retained their affinity with Pro5-, Pro8-, and Ala8-substituents, whereas some loss of affinity was observed in the case of Gly8-Dyn A(1-10).

Topics: Analgesics; Animals; Binding Sites; Binding, Competitive; Brain; Cell Membrane; Dynorphins; Endorphins; Guinea Pigs; Ileum; Male; MSH Release-Inhibiting Hormone; Muscles; Naloxone; Narcotic Antagonists; Oligopeptides; Opioid Peptides; Radioligand Assay; Rats; Receptors, Opioid; Structure-Activity Relationship; Tritium