Dynorphin-(1-13), an Extraordinarily Potent Opioid Peptide

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 76; no. 12; pp. 6666 - 6670
• Main Authors: Goldstein, Avram, Tachibana, S., Lowney, L. I., Hunkapiller, M., Hood, L.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 01.12.1979; National Acad Sciences
• Subjects: Agonists; Amino Acid Sequence; Animals; Antiserum; Bioassay; Biological Assay; Dose-Response Relationship, Drug; Endorphins - isolation & purification; Endorphins - pharmacology; Guinea Pigs; Ileum; Ileum - drug effects; Inhibitory concentration 50; Ligands; Liquid chromatography; Opioid analgesics; Opioid peptides; Radioligand Assay; Rats; Receptors, Opioid - metabolism; Structure-Activity Relationship; Swine; Vas deferens
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.76.12.6666

We describe the opioid properties of a tridecapeptide, the sequence of which corresponds to the NH$_{2}$-terminal sequence of dynorphin, a novel porcine pituitary endorphin. It contains [Leu]enkephalin. In the guinea pig ileum longitudinal muscle preparation it is about 700 times more potent than [Leu]enkephalin. Its effects in this tissue are blocked completely by naloxone, but the apparent affinity of naloxone is $\frac{1}{13}$th that for blockade of [Leu]enkephalin or normorphine. In the mouse vas deferens, this peptide is 3 times more potent than [Leu]enkephalin. Well-washed rat brain membranes degrade the peptide rapidly, suggesting the presence of a membrane-bound degradative enzyme. The peptide displays considerable immunoreactivity in assays with antisera that have been used for the immunohistochemical localization of [Leu]enkephalin. The remarkable enhancement of the potency of [Leu]enkephalin by the COOH-terminal extension -Arg-Arg-Ile-Arg-Pro-Lys-Leu-Lys-OH suggests new interpretations concerning the structure of opiate receptors and the function of the enkephalin pentapeptides.