Document Detail


Modulation of neurotransmitter metabolism by dihydropyridine calcium channel ligands in mouse brain.
MedLine Citation:
PMID:  2449929     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The regional concentrations of dopamine, serotonin, dihydroxyphenylacetic acid, homovanillic acid and 5-hydroxyindole acetic acid were measured in mouse brain following administration of the dihydropyridine calcium channel activator BAY K 8644, and antagonist, nifedipine. BAY K 8644 (1-8 mg/kg) produced dose- and time-dependent increases in dihydroxyphenylacetic acid, homovanillic acid and 5-hydroxyindoleacetic acid concentrations in the caudate, without altering dopamine and serotonin levels. No changes in 5-hydroxyindoleacetic acid concentration were observed in the raphe nuclei, hypothalamus, hippocampus and frontal cortex. Nifedipine (4 mg/kg) blocked BAY K 8644- (2 mg/kg) elicited increases in dihydroxyphenylacetic acid in the caudate. Furthermore, a higher dose of nifedipine (8 mg/kg) decreased dihydroxyphenylacetic acid and homovanillic acid, but did not affect dopamine, serotonin or 5-hydroxyindoleacetic acid concentrations, while a lower dose of nifedipine (2 mg/kg) significantly increased serotonin, 5-hydroxyindoleacetic acid and homovanillic acid, but did not affect dopamine and dihydroxyphenylacetic acid concentrations. The findings that both BAY K 8644 and nifedipine affect neurotransmitter metabolism in vivo in a dose-, time- and brain region-dependent manner, suggest that high-affinity dihydropyridine calcium channel binding sites play an important role in regulating neurotransmitter turnover in the central nervous system.
Authors:
G T Bolger; P Lesieur; A S Basile; P Skolnick
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Brain research     Volume:  438     ISSN:  0006-8993     ISO Abbreviation:  Brain Res.     Publication Date:  1988 Jan 
Date Detail:
Created Date:  1988-04-18     Completed Date:  1988-04-18     Revised Date:  2005-11-17    
Medline Journal Info:
Nlm Unique ID:  0045503     Medline TA:  Brain Res     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  101-7     Citation Subset:  IM    
Affiliation:
Laboratory of Neuroscience, NIDDK, Bethesda, MD 20892.
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MeSH Terms
Descriptor/Qualifier:
3,4-Dihydroxyphenylacetic Acid / metabolism
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / metabolism,  pharmacology*
Animals
Brain / drug effects,  metabolism*
Dihydropyridines / metabolism,  pharmacology*
Dopamine / metabolism
Drug Interactions
Homovanillic Acid / metabolism
Hydroxyindoleacetic Acid / metabolism
Ion Channels / drug effects,  physiology*
Male
Mice
Neurotransmitter Agents / metabolism*
Nifedipine / metabolism,  pharmacology*
Chemical
Reg. No./Substance:
0/Dihydropyridines; 0/Ion Channels; 0/Neurotransmitter Agents; 102-32-9/3,4-Dihydroxyphenylacetic Acid; 21829-25-4/Nifedipine; 306-08-1/Homovanillic Acid; 54-16-0/Hydroxyindoleacetic Acid; 71145-03-4/3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester

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


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