Predominance of the amino-terminal octapeptide fragment of dynorphin in rat brain regions

• DOI: 10.1038/299077a0
• Publication Date: 2004-11-17T21:53:05Z
• Authors: Eckard Weber; Christopher J. Evans; Jack D. Barchas
• Keywords: Dynorphin; Dynorphin A; Endorphins

Dynorphin is a 17 amino acid opioid peptide which was originally isolated and characterized from pig neurohypophysis and gut extracts1–3. It contains a leucine-enkephalin (Leu-enkephalin) sequence at the amino terminus and has an unusually potent in vitro opiate activity in the guinea pig ileum longitudinal muscle/myenteric plexus preparation1–4. Immunohistochemical studies have shown that perikarya, nerve fibres and terminals widely distributed throughout the central nervous system5,6 are immunoreactive for both dynorphin1–17 and α-neo-endorphin6,7, another Leu-enkephalin-containing opioid peptide which is structurally related to dynorphin (Fig. 1) and was isolated from hypothalamus8. But although the regional distributions of α-neo-endorphin and dynorphin1–17 in rat brain, as measured by radioimmunoassay (RIA), are similar, the molar ratio of the two peptides seems to vary greatly from region to region, with α-neo-endorphin being present in much higher concentrations than dynorphini1–17 9–11. We now report that dynorphin1–8, an amino-terminal fragment (Fig. 1), which has only ∼3% of the opioid potency of dynorphin1–17, (ref. 4), is present in up to 10-fold higher concentrations in brain than dynorphhi1–17 immunoreactivity. We further show that dynorphin1–8, but not dynorphin1–17, occurs in approximately equimolar concentrations with α-neo-endorphin in all brain regions examined, suggesting a close biosynthetic relationship between α-neo-endorphin and dynorphin1–8.