Big dynorphin

Where it comes from

Made in

The same neurons as the dynorphins, as an intermediate that is also released

Sent out by

With the dynorphins

Acts on

• Kappa receptors
• NMDA receptors on spinal and hippocampal neurons
• Cell membranes (it can cross them)

What it does

• The most potent of the dynorphins at kappa receptors, and a candidate for the family’s true endogenous ligand ¹
• Its non-opioid action on NMDA receptors may drive the pain and nerve damage of high dynorphin ²
• Crosses cell membranes and leaks them, which dynorphin B does not ³

In medicine

• No medicine copies it, and no laboratory measures it in people
• The kappa medicines act at its receptor, and because it is the most potent natural kappa agonist it is the peptide those medicines are usually compared against in the laboratory ¹

Beyond the body’s own use

• Nothing is in trials. It is a laboratory peptide, used to separate the kappa and the NMDA sides of dynorphin signalling ²
• Its non-opioid action is why it matters: given into the spinal cord it causes pain behaviour through NMDA receptors, which naloxone does not block, so the harm high dynorphin does after spinal injury may not be an opioid effect at all ²
• It also leaks cell membranes directly, a property of the intact 32 residues that disappears once the peptide is cut in two ³