PMID- 15706626 OWN - NLM STAT- MEDLINE DCOM- 20050406 LR - 20131121 IS - 1076-5174 (Print) IS - 1076-5174 (Linking) VI - 40 IP - 2 DP - 2005 Feb TI - Altered extracellular striatal in vivo biotransformation of the opioid neuropeptide dynorphin A(1-17) in the unilateral 6-OHDA rat model of Parkinson's disease. PG - 261-70 AB - The in vivo biotransformation of dynorphin A(1-17) (Dyn A) was studied in the striatum of hemiparkinsonian rats by using microdialysis in combination with nanoflow reversed-phase liquid chromatography/electrospray time-of-flight mass spectrometry. The microdialysis probes were implanted into both hemispheres of unilaterally 6-hydroxydopamine (6-OHDA) lesioned rats. Dyn A (10 pmol microl(-1)) was infused through the probes at 0.4 microl min(-1) for 2 h. Samples were collected every 30 min and analyzed by mass spectrometry. The results showed for the first time that there was a difference in the Dyn A biotransformation when comparing the two corresponding sides of the brain. Dyn A metabolites 1-8, 1-16, 5-17, 10-17, 7-10 and 8-10 were detected in the dopamine-depleted striatum but not in the untreated striatum. Dyn A biotransformed fragments found in both hemispheres were N-terminal fragments 1-4, 1-5, 1-6, 1-11, 1-12 and 1-13, C-terminal fragments 2-17, 3-17, 4-17, 7-17 and 8-17 and internal fragments 2-5, 2-10, 2-11, 2-12, and 8-15. The relative levels of these fragments were lower in the dopamine-depleted striatum. The results imply that the extracellular in vivo processing of the dynorphin system is being disturbed in the 6-OHDA-lesion animal model of Parkinson's disease. CI - Copyright 2005 John Wiley & Sons, Ltd. FAU - Klintenberg, Rebecka AU - Klintenberg R AD - Laboratory for Biological and Medical Mass Spectrometry and Department of Pharmaceutical Biosciences, Uppsala University, Box 583, SE-75123 Uppsala, Sweden. FAU - Andren, Per E AU - Andren PE LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - J Mass Spectrom JT - Journal of mass spectrometry : JMS JID - 9504818 RN - 0 (Peptide Fragments) RN - 74913-18-1 (Dynorphins) RN - 8HW4YBZ748 (Oxidopamine) RN - N21FAR7B4S (Apomorphine) SB - IM MH - Amino Acid Sequence MH - Animals MH - Apomorphine MH - Behavior, Animal/drug effects MH - Brain Chemistry MH - Chromatography, Liquid MH - Corpus Striatum/chemistry/*metabolism MH - Disease Models, Animal MH - Dynorphins/administration & dosage/analysis/*pharmacokinetics MH - Mass Spectrometry/methods MH - Microdialysis MH - Molecular Sequence Data MH - Oxidopamine MH - Parkinson Disease/*metabolism MH - Peptide Fragments/analysis MH - Rats MH - Rats, Sprague-Dawley MH - Spectrometry, Mass, Electrospray Ionization EDAT- 2005/02/12 09:00 MHDA- 2005/04/07 09:00 CRDT- 2005/02/12 09:00 PHST- 2005/02/12 09:00 [pubmed] PHST- 2005/04/07 09:00 [medline] PHST- 2005/02/12 09:00 [entrez] AID - 10.1002/jms.754 [doi] PST - ppublish SO - J Mass Spectrom. 2005 Feb;40(2):261-70. doi: 10.1002/jms.754.