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

Abstract

Dynorphin is a 17 amino acid opioid peptide which was originally isolated and characterized from pig neurohypophysis and gut extracts^1–3. 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 preparation^1–4. Immunohistochemical studies have shown that perikarya, nerve fibres and terminals widely distributed throughout the central nervous system^5,6 are immunoreactive for both dynorphin_1–17 and α-neo-endorphin^6,7, 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 dynorphin_1–17 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 dynorphini_1–17 ^9–11. We now report that dynorphin_1–8, an amino-terminal fragment (Fig. 1), which has only ∼3% of the opioid potency of dynorphin_1–17, (ref. 4), is present in up to 10-fold higher concentrations in brain than dynorphhi_1–17 immunoreactivity. We further show that dynorphin_1–8, but not dynorphin_1–17, occurs in approximately equimolar concentrations with α-neo-endorphin in all brain regions examined, suggesting a close biosynthetic relationship between α-neo-endorphin and dynorphin_1–8.