Dynorphin-(1-13), an extraordinarily potent opioid peptide.

TLDR

The peptide contains the [Leu]enkephalin sequence. The study characterizes the opioid properties of a tridecapeptide matching dynorphin's N‑terminal sequence. The peptide is 700‑fold more potent than [Leu]enkephalin in guinea pig ileum, 3‑fold more potent in mouse vas deferens, its effects are naloxone‑blocked with lower affinity, it is rapidly degraded in rat brain membranes, shows strong immunoreactivity, and its COOH‑terminal extension markedly enhances potency, implying novel insights into opiate receptor structure and enkephalin function.

Abstract

We describe the opioid properties of a tridecapeptide, the sequence of which corresponds to the NH2-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 1/13th 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.