Document Detail


Regulation of DOPA decarboxylase activity in brain of living rat.
MedLine Citation:
PMID:  7643116     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
To test the hypothesis that L-DOPA decarboxylase (DDC) is a regulated enzyme in the synthesis of dopamine (DA), we developed a model of the cerebral uptake and metabolism of [3H]DOPA. The unidirectional blood-brain clearance of [3H]DOPA (K1D) was 0.049 ml g-1 min-1. The relative DDC activity (k3D) was 0.26 min-1 in striatum, 0.04 min-1 in hypothalamus, and 0.02 min-1 in hippocampus. In striatum, 3,4-[3H]dihydroxyphenylacetic acid ([3H]DOPAC) was formed from [3H]DA with a rate constant of 0.013 min-1, [3H]homovanillic acid ([3H]HVA) was formed from [3H]DOPAC at a rate constant of 0.020 min-1, and [3H]HVA was eliminated from brain at a rate constant of 0.037 min-1. Together, these rate constants predicted the ratios of endogenous DOPAC and HVA to DA in rat striatum. Pargyline, an inhibitor of DA catabolism, substantially reduced the contrast between striatum and cortex, in comparison with the contrast seen in autoradiograms of control rats. At 30 min and at 4 h after pargyline, k3D was reduced by 50% in striatum and olfactory tubercle but was unaffected in hypothalamus, indicating that DDC activity is reduced in specific brain regions after monoamine oxidase inhibition. Thus, DDC activity may be a regulated step in the synthesis of DA.
Authors:
P Cumming; H Kuwabara; A Ase; A Gjedde
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of neurochemistry     Volume:  65     ISSN:  0022-3042     ISO Abbreviation:  J. Neurochem.     Publication Date:  1995 Sep 
Date Detail:
Created Date:  1995-09-18     Completed Date:  1995-09-18     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2985190R     Medline TA:  J Neurochem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1381-90     Citation Subset:  IM    
Affiliation:
Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
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MeSH Terms
Descriptor/Qualifier:
3,4-Dihydroxyphenylacetic Acid / metabolism
Animals
Blood-Brain Barrier
Brain / enzymology*
Corpus Striatum / enzymology
Dihydroxyphenylalanine / metabolism
Dopa Decarboxylase / metabolism*
Dopamine / metabolism
Hippocampus / enzymology
Homeostasis
Homovanillic Acid / metabolism
Hypothalamus / enzymology
Kinetics
Male
Olfactory Pathways / enzymology
Pargyline / pharmacology
Rats
Rats, Wistar
Tritium
Chemical
Reg. No./Substance:
10028-17-8/Tritium; 102-32-9/3,4-Dihydroxyphenylacetic Acid; 306-08-1/Homovanillic Acid; 555-57-7/Pargyline; 63-84-3/Dihydroxyphenylalanine; EC 4.1.1.-/Dopa Decarboxylase

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


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