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

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 blo od was studied by matrix-assisted laser desorption/ionization mass spe ctrometry. Biotransformation was observed to produce various opioid an d nonopioid dynorphin A peptides. In this study, in vitro Dyn A (1-17) biotransformation at physiological temperature (37 degrees C) was fou nd 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 wa s the slow removal of tyrosine at position one from Dyn A (1-17) to yi eld 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) an d 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 blo od,undergoing rapid biotransformation. Our results indicate that the r hesus monkey may be a good model for further in vivo pharmacological a nd neurobiological studies.