A dynorphinergic pathway of Leu-enkephalin production in rat substantia nigra

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Abstract
The amino acid sequence of the opioid peptide Leu-enkephalin1–3 is found within several larger peptides4–8, which are generated from the precursors proenkephalin and prodynorphin. Proenkephalin contains four copies of the sequence of Met-enkephalin, a single copy of the sequence of Leu-enkephalin and one copy each of two extended Met-enkephalin sequences9–11. Proenkephalin contains three peptides—α-neo-endorphin, dynorphin A and dynorphin B12—the N-terminal sequences of which are identical to that of Leu-enkephalin. There is good evidence that the large amounts of Leu-enkephalin found in the adrenal medulla are generated from the precursor proenkephalin2,4,13,14, but as yet prodynorphin has not been shown to be processed to yield Leu-enkephalin. We show here that the relatively high levels of Leu-enkephalin found in the rat substantia nigra are supplied by striatonigral axons and generated from the precursor prodynorphin.