In vitro biotransformation of dynorphin A (1-17) is similar in human and rhesus monkey blood as studied by matrix-assisted laser desorption/ionization mass spectrometry

Jim Yu, Eduardo R. Butelman, James H. Woods, Brian T. Chait, Mary Jeanne Kreek

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Dynorphin A (1-17) [Dyn A (1-17)] is an endogenous opioid peptide. In vitro biotransformation of Dyn A (1-17) in human and rhesus monkey blood was studied by matrix-assisted laser desorption/ionization mass spectrometry. Biotransformation was observed to produce various opioid and nonopioid dynorphin A peptides. In this study, in vitro Dyn A (1-17) biotransformation at physiological temperature (37°C) was found to be very similar in human and rhesus monkey blood, although Dyn A (1-17) processing occurred at a faster rate in vitro in monkey blood than in human blood. One dominant pathway in this biotransformation was the slow removal of tyrosine at position one from Dyn A (1-17) to yield the dominant product, Dyn A (2-17). Further slow biotransformation of Dyn A (2-17) also occurred. Another major pathway of Dyn A (1-17) biotransformation is cleavage of the peptide linkage between Arg(6) and Arg(7) to produce the opioid peptide, Dyn A (1-6), and the nonopioid peptide, Dyn A (7-17). These two peptides had a short lifetime in blood, undergoing rapid biotransformation. Our results indicate that the rhesus monkey may be a good model for further in vivo pharmacological and neurobiological studies.

Original languageEnglish (US)
Pages (from-to)507-514
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume279
Issue number2
StatePublished - Nov 1996
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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