Document Detail


The ammonium-induced increase in rat brain lactate concentration is rapid and reversible and is compatible with trafficking and signaling roles for ammonium.
MedLine Citation:
PMID:  17392693     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The glutamate-glutamine shuttle requires a flux of fixed N from neurons to astrocytes. The suggestion that some or all of this N is ammonium has received support from reports that ammonium (as NH(4)(+)) rapidly enters astrocytes. Ammonium might also help control astrocyte energy metabolism by increasing lactate production. If ammonium has these functions, then its effect on brain metabolism must be rapid and reversible. To make a minimal test of this requirement, we have followed the time courses of the changes induced by a 4 min venous infusion of 1 mol/L NH(4)Cl, 2.5 mmol/kg body weight, in rat. Extracellular [NH(4)(+)] in cortex, monitored with ion-selective microelectrodes, reached a peak of approximately 0.7 mmol/L 1.65 mins after the end of the infusion, then recovered. Brain metabolites were monitored non-invasively every 4 mins by (1)H magnetic resonance spectroscopy. Lactate peak area during the 3.2 min acquisition starting at the end of the infusion was 1.84+/-0.24 times baseline (+/-s.e.m., P=0.009, n=9). Lactate increased until 13.2+/-2.1 mins after the end of the infusion and recovered halfway to baseline by 31.2 mins. Glutamate decreased by at least 7.1% (P=0.0026). Infusion of NaCl caused no change in lactate signal. Cerebral blood flow, measured by arterial magnetization labeling, more than doubled, suggesting that the lactate increase was not caused by hypoxia. At least three consecutive ammonium-induced increases in lactate signal could be evoked. The results are compatible with an intercellular trafficking/signaling function for ammonium.
Authors:
Peggy Provent; Nils Kickler; Emmanuel L Barbier; Astrid Bergerot; Régine Farion; Sarah Goury; Païkan Marcaggi; Christoph Segebarth; Jonathan A Coles
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-03-28
Journal Detail:
Title:  Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism     Volume:  27     ISSN:  0271-678X     ISO Abbreviation:  J. Cereb. Blood Flow Metab.     Publication Date:  2007 Nov 
Date Detail:
Created Date:  2007-10-23     Completed Date:  2007-11-19     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8112566     Medline TA:  J Cereb Blood Flow Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1830-40     Citation Subset:  IM    
Affiliation:
INSERM, UMR-S 836, Grenoble Institut des Neurosciences, Grenoble, France.
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MeSH Terms
Descriptor/Qualifier:
Ammonium Chloride / pharmacology
Animals
Astrocytes / metabolism
Brain Chemistry / drug effects*
Cerebrovascular Circulation / physiology
Data Interpretation, Statistical
Electrodes, Implanted
Extracellular Space / drug effects,  metabolism
Glutamic Acid / isolation & purification,  metabolism
Homeostasis / physiology
Image Processing, Computer-Assisted
Lactic Acid / metabolism*
Magnetic Resonance Spectroscopy
Male
Neurons / metabolism
Potassium / metabolism
Quaternary Ammonium Compounds / pharmacology*
Rats
Rats, Wistar
Signal Transduction / drug effects,  physiology*
Sodium Chloride / pharmacology
Vascular Resistance / drug effects,  physiology
Vasodilation / physiology
Chemical
Reg. No./Substance:
0/Quaternary Ammonium Compounds; 12125-02-9/Ammonium Chloride; 50-21-5/Lactic Acid; 56-86-0/Glutamic Acid; 7440-09-7/Potassium; 7647-14-5/Sodium Chloride

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


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