Dynorphin A(1-13)

Dynorphin A(1-13), a tridecapeptide of the endogenous opioid peptides, has modest effects in reducing mild opiate withdrawal in humans. The therapeutic potential of dynorphin A(1–13) is limited due to extensive metabolism by human metabolic enzymes resulting in an in vivo half-life of less than one minute. Chemical modifications of dynorphin A(1–13), such as N-methylation of Tyr1 and amidation of the C-terminus have been shown to be effective in protecting against the proteolytic enzymes in human plasma. This article is a general review of the metabolism of dynorphin A(1–13) in human plasma and CSF. >> Read More

Dynorphin A is an endogenous opioid peptide that preferentially activates κ opioid receptors and is antinociceptive at physiological concentrations. Levels of dynorphin A and a major metabolite, dynorphin A (1-13), increase significantly following spinal cord trauma and reportedly contribute to neurodegeneration associated with secondary injury. Interestingly, both κ opioid and N-methyl-D-aspartate (NMDA) receptor antagonists can modulate dynorphin toxicity, suggesting that dynorphin is acting (directly or indirectly) through κ opioid and/or NMDA receptor (NMDAR) types. Despite these findings, few studies have systematically explored dynorphin toxicity at the cellular level in defined populations of neurons co-expressing κ opioid and NMDA receptors.

Hauser, K. F., Foldes, J. K., & Turbek, C. S. (1999). Dynorphin A (1–13) neurotoxicity in vitro: opioid and non-opioid mechanisms in mouse spinal cord neurons. Experimental neurology, 160(2), 361-375.

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.

Goldstein, A., Tachibana, S., Lowney, L. I., Hunkapiller, M., & Hood, L. (1979). Dynorphin-(1-13), an extraordinarily potent opioid peptide. Proceedings of the National Academy of Sciences, 76(12), 6666-6670.