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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
Author(s) -
Klintenberg Rebecka,
Andrén Per E.
Publication year - 2005
Publication title -
journal of mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 121
eISSN - 1096-9888
pISSN - 1076-5174
DOI - 10.1002/jms.754
Subject(s) - chemistry , microdialysis , dynorphin , striatum , in vivo , dynorphin a , dopamine , metabolite , substantia nigra , extracellular , endocrinology , opioid , biochemistry , opioid peptide , dopaminergic , medicine , receptor , microbiology and biotechnology , biology
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 µl −1 ) was infused through the probes at 0.4 µl 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. Copyright © 2005 John Wiley & Sons, Ltd.