Des-enkephalin-γ-endorphin (DEγE): Biotransformation in rat, dog and human plasma

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Abstract
Biotransformation of [3H-Lys9] DEΓE was investigated afterin vitro incubation of the tritiated peptide with rat, dog and human plasma. In addition, its metabolite profile in blood was studied following intravenous administration to rats and dogs. Half-lives for thein vitro disappearance of DEΓE in plasma were 13.0±0.8 min (dog), 15.7±1.2 min (rat) and 19.2±0.9 min (human), indicating very rapid degradation of the peptide by proteolytic enzymes. Biotransformation products were identified on the basis of co-chromatography on HPLC with synthetic reference peptides. The six principal fragments appeared to be β-endorphin (βE) sequences 7–17, 8–17, 9–17, 6–15, 7–15 and 8–15. The abundance of βE6–15, βE7–15 and βE8–15 in rat and human plasma suggests preferential, subsequent carboxypeptidase and aminopeptidase mechanisms, whereas in dog plasma DEΓE is predominantly degraded by aminopeptidase activities (major peptide metabolites: βE7–17 and βE8–17). In thein vivo studies with rats and dogs the same radioactive peptide fragments were detected in blood as found in thein vitro experiments with plasma. In both species their blood levels were already maximal within a minute after intravenous administration of the parent peptide, thereafter they declined rapidly.3H-Lysine was the main radioactive metabolitein vivo, exceeding 70% of total radioactivity in rat and dog blood 10 min after3H-DEΓE dosing.

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