Yu J, Butelman E R, Woods J H, Chait B T, Kreek M J
Laboratory of Biology of Addictive Disease, Rockefeller University, New York, New York, USA.
J Pharmacol Exp Ther. 1996 Nov;279(2):507-14.
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.
强啡肽A（1-17）[Dyn A（1-17）]是一种内源性阿片肽。采用基质辅助激光解吸/电离质谱法研究了强啡肽A（1-17）在人和恒河猴血液中的体外生物转化。观察到生物转化产生了各种阿片类和非阿片类强啡肽A肽。在本研究中，发现在生理温度（37℃）下，强啡肽A（1-17）在人和恒河猴血液中的体外生物转化非常相似，尽管强啡肽A（1-17）在体外猴血中的加工速度比人血中快。这种生物转化的一个主要途径是从强啡肽A（1-17）中缓慢去除第1位的酪氨酸，以产生主要产物强啡肽A（2-17）。强啡肽A（2-17）也发生了进一步的缓慢生物转化。强啡肽A（1-17）生物转化的另一个主要途径是切割精氨酸（6）和精氨酸（7）之间的肽键，产生阿片肽强啡肽A（1-6）和非阿片肽强啡肽A（7-17）。这两种肽在血液中的寿命较短，会迅速发生生物转化。我们的结果表明，恒河猴可能是进一步进行体内药理学和神经生物学研究的良好模型。
