Document Detail


Formation and clearance of interstitial metabolites of dopamine and serotonin in the rat striatum: an in vivo microdialysis study.
MedLine Citation:
PMID:  1383428     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In vivo microdialysis was employed in order to characterize the steady-state kinetics of the turnover of specific dopamine and serotonin metabolites in the rat striatum 48 h after surgery. Inhibitors of monoamine oxidase (MAO; pargyline) and catechol-O-methyltransferase (COMT; Ro 40-7592) were administered, either separately or in conjunction, at doses sufficient to block these enzymes in the CNS. In some experiments, the acid metabolite carrier was blocked with probenecid. Temporal changes were then observed in the efflux of interstitial dopamine, 3-methoxytyramine (3-MT), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA). The fractional rate constants for the accumulation or disappearance of the metabolites could be determined after pharmacological blockade of catabolic enzymes or the acid metabolite carrier. Interstitial 5-HIAA was found to be cleared with a half-life of approximately 2 h. After blockade of either MAO or COMT, HVA disappeared with a half-life of 17 min. Experiments employing probenecid suggested that some of the interstitial HVA was cleared by the acid metabolite carrier, the remainder being cleared by a probenecid-insensitive process, possibly conjugation. After MAO inhibition, DOPAC disappeared with an apparent half-life of 11.3 min. The rate of 3-MT accumulation after pargyline indicated that the majority of interstitial HVA (> 95%) is formed from DOPAC rather than 3-MT. The formation of 3-MT from interstitial dopamine, calculated from the accumulation rate of 3-MT after pargyline, appeared to follow first-order kinetics (k = 0.1 min-1).
Authors:
P Cumming; E Brown; G Damsma; H Fibiger
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of neurochemistry     Volume:  59     ISSN:  0022-3042     ISO Abbreviation:  J. Neurochem.     Publication Date:  1992 Nov 
Date Detail:
Created Date:  1992-11-20     Completed Date:  1992-11-20     Revised Date:  2013-11-25    
Medline Journal Info:
Nlm Unique ID:  2985190R     Medline TA:  J Neurochem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1905-14     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Benzophenones / pharmacology
Catechol O-Methyltransferase / antagonists & inhibitors
Corpus Striatum / metabolism*
Dialysis* / methods
Dopamine / metabolism*
Drug Combinations
Extracellular Space / metabolism*
Hydroxyindoleacetic Acid / metabolism
Male
Nitrophenols
Pargyline / pharmacology
Probenecid / pharmacology
Rats
Rats, Wistar
Serotonin / metabolism*
Chemical
Reg. No./Substance:
0/Benzophenones; 0/Drug Combinations; 0/Nitrophenols; 333DO1RDJY/Serotonin; 54-16-0/Hydroxyindoleacetic Acid; 9MV14S8G3E/Pargyline; CIF6334OLY/tolcapone; EC 2.1.1.6/Catechol O-Methyltransferase; PO572Z7917/Probenecid; VTD58H1Z2X/Dopamine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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