DYNORPHIN-(1-13), AN EXTRAORDINARILY POTENT OPIOID PEPTIDE

The opioid properties of a tridecapeptide, the sequence of which corresponds to the NH2-terminal sequence of dynorphin (a novel porcine pituitary endorphin) was described. It contains [Leu]enkephalin. In the guinea pig ileum longitudinal muscle preparation, it is .apprx. 700 times more potent than [Leu]enkephalin. Its effects in this tissue are blocked completely by naloxone, but the apparent affinity of naloxone is 1/13 that for blockade of [Leu]enkephalin or normorphine. In the mouse vas deferens, the 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.