Document Detail


Effects of 3-nitropropionic acid on synaptosomal energy and transmitter metabolism: relevance to neurodegenerative brain diseases.
MedLine Citation:
PMID:  7914221     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
3-Nitropropionic acid (3-NPA) inhibited synaptosomal respiration in a dose-dependent manner; the degree of inhibition by the same concentration of the compound was greater, however, when respiration was stimulated by concomitant increase in ATP usage. The most rapid event after addition of 3-NPA was a decrease in [creatine phosphate]/[creatine] ([CrP]/[Cr]) and an increase in [lactate]/[pyruvate]. A fall in [ATP]/[ADP] and [GTP]/[GDP] was initially less pronounced but closely followed that in [CrP]/[Cr]. In the absence of glutamine, 3-NPA caused a pronounced decrease in internal aspartate level and a small reduction in glutamate concentration, whereas [GABA] rose; the sum of these three amino acids inside synaptosomes fell, but there were no increases in their external levels. With glutamine in the medium, the reduction in intrasynaptosomal aspartate was accompanied by increases in intrasynaptosomal glutamate and GABA. The external concentration of glutamate rose substantially in the presence of the inhibitor. 3-NPA had no effect on basal release of either glutamate (and GABA) or biogenic amines but increased efflux occurring upon addition of nonsaturating concentrations of the depolarizing agents veratridine and KCl. The results allow the following predictions with respect to the behavior of brain metabolism in neurodegenerative diseases that involve restrictions of mitochondrial function: (1) The extent of inhibition of mitochondrial ATP generation is expected to be greater in cells with high energy demand. The earliest signs of impairment of the respiratory chain function are a fall in [PCr]/[Cr] (or a rise in [Pi]/[CrP]) and an increase in [lactate]/[pyruvate]. (2) A fall in [GTP]/[GDP] can limit protein synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
Authors:
M Erecińska; D Nelson
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of neurochemistry     Volume:  63     ISSN:  0022-3042     ISO Abbreviation:  J. Neurochem.     Publication Date:  1994 Sep 
Date Detail:
Created Date:  1994-09-08     Completed Date:  1994-09-08     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2985190R     Medline TA:  J Neurochem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1033-41     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, University of Pennsylvania, Philadelphia.
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphate / metabolism
Animals
Brain Diseases / metabolism*,  pathology
Cell Death
Creatine / metabolism
Energy Metabolism / drug effects*
Glutamates / metabolism
Glutamic Acid
Glutamine / pharmacology
Guanosine Diphosphate / metabolism
Guanosine Triphosphate / metabolism
Lactates / metabolism
Lactic Acid
Male
Neurotransmitter Agents / metabolism*
Nitro Compounds
Oxygen Consumption / drug effects
Phosphocreatine / metabolism
Propionic Acids / pharmacology*
Pyruvates / metabolism
Pyruvic Acid
Rats
Rats, Sprague-Dawley
Synaptosomes / drug effects,  metabolism*
gamma-Aminobutyric Acid / metabolism
Grant Support
ID/Acronym/Agency:
NS 28329/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Glutamates; 0/Lactates; 0/Neurotransmitter Agents; 0/Nitro Compounds; 0/Propionic Acids; 0/Pyruvates; 127-17-3/Pyruvic Acid; 146-91-8/Guanosine Diphosphate; 50-21-5/Lactic Acid; 504-88-1/3-nitropropionic acid; 56-12-2/gamma-Aminobutyric Acid; 56-65-5/Adenosine Triphosphate; 56-85-9/Glutamine; 56-86-0/Glutamic Acid; 57-00-1/Creatine; 67-07-2/Phosphocreatine; 86-01-1/Guanosine Triphosphate

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


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