Document Detail

Protein kinase G is involved in ammonia-induced swelling of astrocytes.
MedLine Citation:
PMID:  19393034     Owner:  NLM     Status:  MEDLINE    
Ammonia-induced swelling of astrocytes is a primary cause of brain edema associated with acute hepatic encephalopathy. Previous studies have shown that ammonia transiently increases cGMP in brain in vivo and in cultured astrocytes in vitro. We hypothesized that protein kinase G (PKG), an enzyme activated by cGMP and implicated in regulation of cell shape, size, and/or volume in peripheral and CNS cells, may play a role in the ammonia-induced astrocytic volume increase. Treatment of cultured rat cortical astrocytes with 1 or 5 mM NH4Cl (ammonia) for 24 h increased their cell volume by 50% and 80% above control, respectively, as measured by confocal imaging followed by 3D computational analysis. A cGMP analog, 8-(4-chlorophenylthio)-cGMP, increased the cell volume in control cells and potentiated the increase in 1 mM ammonia-treated cells. A soluble guanylate cyclase inhibitor (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one) abrogated, and a PKG inhibitor [8-(4-chlorophenylthio)-cGMP-thioate, Rp-isomer] dose-dependently reduced the cell volume-increasing effect of 5 mM ammonia. The results suggest that (i) PKG may play a permissive role in ammonia-induced astrocytic swelling and (ii) elevation of brain cGMP associated with acute exposure to ammonia in vivo may aggravate the ensuing brain edema.
Agnieszka Konopacka; Filip A Konopacki; Jan Albrecht
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of neurochemistry     Volume:  109 Suppl 1     ISSN:  1471-4159     ISO Abbreviation:  J. Neurochem.     Publication Date:  2009 May 
Date Detail:
Created Date:  2009-04-27     Completed Date:  2009-05-21     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  2985190R     Medline TA:  J Neurochem     Country:  England    
Other Details:
Languages:  eng     Pagination:  246-51     Citation Subset:  IM    
Department of Neurotoxicology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.
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MeSH Terms
Ammonia / toxicity*
Astrocytes / drug effects*,  enzymology*,  pathology
Brain Edema / pathology
Calcium Channel Blockers / pharmacology
Calcium Channels, L-Type / drug effects,  physiology
Calcium Signaling / drug effects
Cell Size
Cells, Cultured
Cyclic GMP / analogs & derivatives,  pharmacology
Cyclic GMP-Dependent Protein Kinases / antagonists & inhibitors,  physiology*
Enzyme Inhibitors / pharmacology
Fluorescent Dyes
Guanylate Cyclase / antagonists & inhibitors
Microscopy, Confocal
Nimodipine / pharmacology
Rats, Wistar
Thionucleotides / pharmacology
Reg. No./Substance:
0/Calcium Channel Blockers; 0/Calcium Channels, L-Type; 0/Enzyme Inhibitors; 0/Fluorescent Dyes; 0/Thionucleotides; 54364-02-2/8-((4-chlorophenyl)thio)cyclic-3',5'-GMP; 66085-59-4/Nimodipine; 7664-41-7/Ammonia; 7665-99-8/Cyclic GMP; EC GMP-Dependent Protein Kinases; EC Cyclase

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

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