Brain tissue converts dynorphin (a kappa opioid) into leu-enkephalin (a delta opioid) via a metalloendopeptidase, effectively switching opioid signaling from one receptor type to another.
60% conversion rateWith competing enzymes blocked, 60% of dynorphin A(1-8) was converted to leu-enkephalin — switching from kappa to delta opioid signaling
What the researchers found
Dynorphin A(1-8) is extensively converted to leu-enkephalin by metalloendopeptidase EC 3.4.24.15 across all brain regions, effectively switching opioid signaling from kappa to delta receptors.
Why it matters
This shows the brain can actively convert one opioid signal into another. A kappa-receptor signal (dynorphin) becomes a delta-receptor signal (enkephalin), switching the type of opioid effect.
How the study worked
Radiolabeled dynorphin A(1-8) was incubated with rat brain tissue. Products were identified by HPLC. Enzyme characteristics were determined using specific inhibitors and substrates of varying length.
What this study cannot tell us
In-vitro tissue study. The enzyme's actual contribution in living brain tissue, where many enzymes compete, is unknown. High doses of peptidase inhibitors were needed.
How to read the evidence
Preliminary in-vitro study using radiolabeled peptides. Demonstrates an enzymatic pathway but its quantitative importance in living brain requires validation.
When this study was published
Published in 1990. The concept of opioid peptide interconversion has been further developed and is now recognized as an important aspect of opioid signaling regulation.
The bigger picture
This revealed that the brain's opioid system is more dynamic than a simple lock-and-key model. The brain doesn't just release fixed signals — it can transform them mid-transit, switching the type of opioid effect. This adds a layer of complexity to opioid pharmacology and could explain unexpected effects of opioid drugs.
Questions still open
- Is this conversion pathway altered in chronic pain or opioid tolerance?
- Could targeting this converting enzyme shift opioid signaling to favor specific therapeutic effects?
Common questions
What difference does it make whether dynorphin or enkephalin is active?
Why is this conversion important?
Read the original research
Formation of [Leu5]enkephalin from dynorphin A(1-8) by rat central nervous tissue in vitro.
Journal of neurochemistry, 54(4), 1379-85
Citation
Dixon, D M; Traynor, J R. (1990). Formation of [Leu5]enkephalin from dynorphin A(1-8) by rat central nervous tissue in vitro.. Journal of neurochemistry, 54(4), 1379-85.