title: 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.
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 degrees 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.
authors.affiliation: Laboratory of Biology of Addictive Disease, Rockefeller University, New York, New York, USA.
authors.forename: J
authors.initials: J
authors.lastname: Yu
authors.forename: E R
authors.initials: ER
authors.lastname: Butelman
authors.forename: J H
authors.initials: JH
authors.lastname: Woods
authors.forename: B T
authors.initials: BT
authors.lastname: Chait
authors.forename: M J
authors.initials: MJ
authors.lastname: Kreek
mesh_terms: D000328:Adult; D000818:Animals; D001711:Biotransformation; D002138:Calibration; D004399:Dynorphins / Q000493:pharmacokinetics* / Q000494:pharmacology; D005260:Female; D006801:Humans; D008253:Macaca mulatta; D008297:Male; D008875:Middle Aged; D013045:Species Specificity; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013696:Temperature
chemical_list: D004399:Dynorphins