Does acute glutamine depletion enhance the response of glutamine synthesis to fasting in muscle in adult and old rats?

• Published in: Clinical nutrition (Edinburgh, Scotland) Scotland), 2005-06, Vol.24 (3), p.398-406
• Main Authors: Meynial-Denis, Dominique, Verdier, Lionel, Mignon, Michelle, Leclerc, Jean-Noël, Bayle, Gérard, Darmaun, Dominique
• Format: Article
• Language: English
• Subjects: Age Factors; Aging; Animals; Biological and medical sciences; Catabolic state; Chelating Agents - pharmacology; Fasting - blood; Fasting - metabolism; Glutamate-Ammonia Ligase - metabolism; Glutamine - analogs & derivatives; Glutamine - biosynthesis; Glutamine - blood; Glutamine - deficiency; Glutamine - metabolism; Glutamine - urine; Glutamine production; Life Sciences; Male; Medical sciences; Metabolic diseases; Muscle, Skeletal - enzymology; Muscle, Skeletal - metabolism; Phenylbutyrates - pharmacology; Rat; Rats; Rats, Wistar; Skeletal muscle
• ISSN: 0261-5614; 1532-1983
• DOI: 10.1016/j.clnu.2004.12.004

Background and aims: In earlier studies, skeletal muscle glutamine synthetase (GS) activity was shown to be enhanced by fasting and glucocorticoids, and inhibited by exogenous glutamine (Gln) supplementation. The current study was designed to determine whether phenylbutyrate (ΦB), a Gln-chelating agent in humans, (1) could trap Gln and produce a decline in plasma Gln in rats, as it does in humans, and (2) if so, whether ΦB would further enhance the response of muscle GS activity to fasting in rats. Methods: Adult (6–8 months) and aged (20–21 months) rats were fasted for 5 days and received two doses of 0.5 g ΦB by orogastric route at times 0 and 4 h, and were then sacrificed at 5.5 h. Plasma Gln was measured by enzymatic methods, other amino acids were quantified by amino acid analysis. GS activity was measured in soleus (SO) and tibialis anterior (TA) muscles. Results: ΦB treatment was associated with: (1) a 20% decline in plasma Gln concentration from 572±54 to 424±34 μmol/L ( P < 0.05 ) and from 476±49 to 360±80 μmol/L ( P < 0.05 ) in fasted adult and old rats, respectively; and (2) a preservation of GS up-regulation by fasting in TA and SO muscles in both adult and aged rats, with TA muscle GS activities of 198±65 vs. 203±68 (ΦB-treated vs. vehicle-treated, NS), and 244±81 vs. 274±59 (NS) nmol/h/mg protein in adult and aged rats, respectively. Conclusion: These data suggest that: (1) large doses of ΦB deplete plasma Gln in fasted rats, regardless of age, (2) Gln depletion induced by ΦB does not alter GS activity.