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Suppression of glial glutamine release to the extracellular fluid studied in vivo by NMR and microdialysis in hyperammonemic rat brain
Author(s) -
Kanamori Keiko,
Ross Brian D.
Publication year - 2005
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2005.03170.x
Subject(s) - glutamine , microdialysis , extracellular , in vivo , extracellular fluid , chemistry , biochemistry , medicine , choline , glutamate receptor , endocrinology , intracellular ph , amino acid , biology , receptor , microbiology and biotechnology
Release of glial glutamine (GLN) to the extracellular fluid (ECF), mainly mediated by the bidirectional system N transporter SN1, was studied in vivo in hyperammonemic rat brain, using 15 N‐nuclear magnetic resonance (NMR) to monitor intracellular [5‐ 15 N]GLN and microdialysis/gradient 1 H‐ 15 N heteronuclear single‐quantum correlation NMR to analyse extracellular [5‐ 15 N]GLN. GLN ECF was elevated to 2.4 ± 0.2 m m after 4.5 h of intravenous ammonium acetate infusion. The [GLN i ]/[GLN ECF ] ratio (i = intracellular) was 9.6 ± 0.9, compared with 17–20 in normal brain. GLN ECF then decreased substantially at t = 4.9 ± 0.1 h. Comparison of the time‐courses of intra‐ and extra‐cellular [5‐ 15 N]GLN strongly suggested that the observed decrease reflects partial suppression of glial GLN release to ECF. Suppression also followed elevation of GLN ECF to 1.9 m m , resulting in a [GLN] i /[GLN ECF ] ratio of 8.4, upon perfusion of α ‐(methylamino)isobutyrate which inhibits neuronal uptake of GLN ECF mediated by sodium‐coupled amino acid transporter (SAT). The results provide first evidence for bidirectional operation of SN1 in vivo , and clarify the effect of transmembrane GLN gradient on glial GLN release at physiological Na + gradient. Implications of the results for SN1 as an additional regulatory site in the glutamine/glutamate cycle and utility of this approach for examining the role of GLN in an experimental model of fulminant hepatic failure are discussed.