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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
Pt 13
pubmed:dateCreated
2010-6-14
pubmed:abstractText
Glutamine synthetase (GSase), the enzyme that catalyses the conversion of glutamate and ammonia to glutamine, is present at high levels in vertebrate brain tissue and is thought to protect the brain from elevated ammonia concentrations. We tested the hypothesis that high brain GSase activity is critical in preventing accumulation of brain ammonia and glutamate during ammonia loading in the ammonia-intolerant rainbow trout. Trout pre-injected with saline or the GSase inhibitor methionine sulfoximine (MSOX, 6 mg kg(-1)), were exposed to 0, 670 or 1000 micromol l(-1) NH(4)Cl in the water for 24 and 96 h. Brain ammonia levels were 3- to 6-fold higher in ammonia-exposed fish relative to control fish and MSOX treatment did not alter this. Brain GSase activity was unaffected by ammonia exposure, while MSOX inhibited GSase activity by approximately 75%. Brain glutamate levels were lower and glutamine levels were higher in fish exposed to ammonia relative to controls. While MSOX treatment had little impact on brain glutamate, glutamine levels were significantly reduced by 96 h. With ammonia treatment, significant changes in the concentration of multiple other brain amino acids occurred and these changes were mostly reversed or eliminated with MSOX. Overall the changes in amino acid levels suggest that multiple enzymatic pathways can supply glutamate for the production of glutamine via GSase during ammonia exposure and that alternative transaminase pathways can be recruited for ammonia detoxification. Plasma cortisol levels increased 7- to 15-fold at 24 h in response to ammonia and MSOX did not exacerbate this stress response. These findings indicate that rainbow trout possess a relatively large reserve capacity for ammonia detoxification and for preventing glutamate accumulation during hyperammonaemic conditions.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1477-9145
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
213
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2343-53
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Inhibition of glutamine synthetase during ammonia exposure in rainbow trout indicates a high reserve capacity to prevent brain ammonia toxicity.
pubmed:affiliation
Department of Integrative Biology, University of Guelph, 488 Gordon Street, Guelph, ON, Canada, N1G 2W1.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't